vam bulletin 22...an lgc publication in support of the national measurement system issue nº 22...

A n L G C p u b l i c a t i o n i n s u p p o r t o f t h e N a t i o n a l M e a s u r e m e n t S y s t e m I s s u e N ordm 2 2 S p r i n g 2 0 0 0

VAM BULLETIN

Traceable measurements A different route to reliable analytical dataMethods for testing E coliVAM and the measurement issues related to QUIDThe reliability of mass spec for identification purposesUltrafine particles and air quality control

Contents

2 V A M B U L L E T I N

C O N T E N T S

Cover photograph by Andrew Brookes

Alison GillespieKeith MarshallEditors

General enquiries about VAM toVAM Helpdesk 020 8943 7393vamlgccouk

LGCrsquos addressLGCQueens RoadTeddingtonMiddlesex TW11 0LY

The DTI VAM programme

The DTIrsquos programme on ValidAnalytical Measurement (VAM) is anintegral part of the UK NationalMeasurement System The VAMprogramme aims to help analyticallaboratories demonstrate the validity oftheir data and to facilitate mutualrecognition of the results of analyticalmeasurements

The VAM programme sets out thefollowing six principles of good analyticalpractice backed up by technical supportand management guidance to enablelaboratories to deliver reliable resultsconsistently and thereby improveperformance

1 Analytical measurements should bemade to satisfy an agreed requirement

2 Analytical measurements should bemade using methods and equipmentwhich have been tested to ensure theyare fit for their purpose

3 Staff making analytical measurementsshould be both qualified and competentto undertake the task

4 There should be a regular independentassessment of the technical performanceof a laboratory

5 Analytical measurements made in onelocation should be consistent with thoseelsewhere

6 Organisations making analyticalmeasurements should have well definedquality control and quality assuranceprocedures

Editorial

Traceable measurements A different route to reliable analytical data 3

Guest column

Methods for testing Escherichia coli 5

Focus on sectors

VAM and the measurement issues related to QUID7

Contributed articles

The reliability of mass spec for identification purposes 12

Ultrafine particles and air quality control14

Spectra in quantitative chemical analysis I Smoothing to reduce noise 18

Case study

Titanium dioxide manufacture A microcosm of analytical best practice 23

VAM in education

Resource for Quality Assurance of chemical measurements 27

Reference materials update 28

VAM news

VAM 2000ndash03 29

New international standard for the operation of laboratories30

CITAC Secretariat moves to Belgium 31

Measurement testing and calibration evidence routes for NVQsSVQs32

International collaboration32

VAM products and services 32

Chemical nomenclature

The meaning of units33

Forthcoming events34

Web links 35

Contact points 36

Traceable measurements A different route to reliableanalytical data


E D I T O R I A L

Mike SargentLGC

Analytical measurements play a critical role in todayrsquos society

and in manufacturing industry The demandfor analysis continues ever upward oneestimate by DTI in 19961 suggested that thetotal value of chemical analysis in the UKwas as high as pound7 billion pa The same studyalso highlighted the key issue facinganalytical laboratories constant commercialpressure to do more for less in a shorter timewhilst simultaneously providing customersclients and regulators with ever morerigorous evidence that their data is bothreliable and comparable with resultsobtained by other laboratories companies orcountries Annual surveys2 of the trendsidentified in 1996 show that they arecontinuing

LGC like other commerciallaboratories is affected by these trendsHowever as the UK centre for analyticalscience LGC has also been working for thepast six years with national laboratoriesaround the world to develop a more costeffective approach for achieving reliable andcomparable analytical results Some earlyapplications in areas as diverse as clinicalanalysis adulteration of foods and metalspeciation have been described in the VAMBulletin3-5 As we enter a new millennium itis timely to review why a significant newdevelopment for analytical laboratories isneeded and what must be done to achieve it

In the longer term the work at LGCunderpins an international goal of modifyingthe approach widely used to achieve reliablephysical measurements (eg length masstime) so that it can be used in chemistryPhysical measurements often depend onaccurate calibration of the measurementinstrument using traceable measurement

standards How this can be applied toanalytical chemistry is not alwaysimmediately apparent All analysts areaware however that much effort is requiredin addition to instrument calibration in orderto obtain results which are comparable andfit for purpose

Accurate and comparable physicalmeasurements are achieved by ensuring thateach measurement result for a particularparameter is traceable to a unique referencewhich is accepted throughout the worldThis reference may be an artefact such as theinternational standard kilogram or morelikely today the relevant SI unit most ofwhich are based on a quantum phe-nomenon In either case the concept oftraceability depends on a chain ofmeasurements linked back to the appropriateinternational primary standard through aseries of calibrations (ie comparisonsbetween two standards in the chain) Providedthe uncertainties of the comparisons areknown a measurement result obtainedthrough calibration against one of thesestandards will itself be traceable to theagreed reference

Analytical measurementsplay a critical role in todayrsquos society

Calibration in this way using chemicalstandards is complicated by the dependenceof the chemical measurement process on thesample matrix The measurement does notusually take place directly on the originalsample and the instrumental determinationis often the final step of a complex analyticalmethod involving extensive pretreatment ofthe sample Hence calibration of theinstrument alone is insufficient to achievereliable and comparable results Thus thereare relatively few traceable chemicalmeasurement standards in the sense used forphysical measurement standards and the

concept of traceable measurements is notwidely known by analysts

The chemical matrix problem hasstimulated the development of twoadditional approaches to achieving reliableand comparable chemical measurementsmatrix reference materials and inter-laboratory comparisons The matrix-matched certified reference material (CRM)is a unique type of chemical standardcommonly used to validate completemeasurement methods and sometimes forinstrumental calibration (eg in XRF) Suchstandards are prepared to correspond toeach required analytematrix combinationSimilarly inter-laboratory comparisons areundertaken for each relevant analytematrixcombination in order to establishcomparability of their measurement dataThese comparisons range from lsquoround-robinrsquostudies which collaboratively test a newmethod to formal proficiency testing (PT)schemes which assess agreement betweenlaboratories on an on-going basis

CRMs and PT schemes have been usedwith reasonable success over many years butthey both have a number of technicalpractical and economic limitations Theneed for a wide variety of application-specific CRMs has lead to fragmentedproduction without any formal relationshipbetween the certified values of CRMsproduced for different applications or bydifferent organisations There are thousandsof CRMs in use but many of those requiredfor critical applications such as manu-facturing trade health or the environmentare unavailable In addition productioncosts are high and it is difficult or impossibleto manufacture sufficiently stable CRMs forsome applications Inter-laboratorycomparisons also have a number oflimitations particularly that they are time-consuming and expensive Comparabilityusually extends only to the immediateparticipants in a single comparison because

comparability between different comparisonsis rarely established even when they are co-ordinated by the same organisation It isimpracticable to organise comparisons forevery routine application or to organise aworldwide comparison involving all thelaboratories requiring comparability for eachmeasurement application

These problems have long beenrecognised as a significant technical andeconomic limitation in delivering soundchemical measurement data The situation issteadily worsening with increasing demandfrom purchasers of data and by regulatorsfor proven comparability of measurementsThis is for several reasons Global expansionof trade means more countries and morelaboratories need to be brought into eachinter-laboratory comparison In additionincreasing numbers of measurements areused in support of regulations for whichthere is an expanding requirement forrigorously proven reliability and comparabilityFinally increasing use of sub-contractedmeasurements due to commercial pressureson laboratories requires not only conformityof contractors to quality systems but alsodemonstration of the comparability of datafrom different contractors

The application of metrologicalprinciples in chemistry offers a potentialmeans of addressing the situation but severalorganisational and scientific problems needto be overcome In most countriesgovernmental expertise in chemicalmeasurement is more widely dispersed thanis the case for physical measurements whichare mainly focused on a single NationalMeasurement Institute (NMI) From atechnical standpoint the uncertainty of thesample preparation and pre-treatment islargely an empirical estimate and theuncertainty associated with taking the initialsample or sub-sample is often overlookedTraceable measurements can however onlybe achieved when the uncertainty of theentire chemical measurement procedure isfully understood Developing referencemethods which offer improved andrigorously determined levels of uncertaintyfor difficult sample matrices is a key factorin solving this problem67

In order to address both the technicaland organisational problems theInternational Committee for Weights andMeasures (CIPM) decided in 1993 to

establish an international collaborativeprogramme of work in chemistry7 Thisprogramme is organised through the CIPMrsquosConsultative Committee on Amount ofSubstance (CCQM) The CCQM aims toresolve the practical difficulties of achievingcomparable chemical measurements throughtraceability and to provide an internationalstructure which will depend on a chain ofnational and regional laboratories Thesewill in turn demonstrate the equivalence of their measurement data throughmeasurement comparisons as well asimplementing a quality management systemfor their calibration or measurementcertificates The CCQM and regionalmetrology organisations will organise a seriesof key comparisons which reflect applicationsrelevant to industry trade healthenvironment etc and will not comprise just measurements on single substances and standards

NMIs around the world are contributingto the development and implementation ofkey comparisons in all areas of metrologyand formalising arrangements to link themto calibration and field laboratories Theseformal arrangements are set out in a MutualRecognition Arrangement (MRA) co-ordinated by the International Bureau ofWeights and Measures (BIPM) in Paris Inthe case of chemistry links to the keycomparisons will be achieved throughprovision of traceable CRMs standards andcalibration services and development ofproficiency testing (PT) schemes based ontraceable reference values The UK nationalmeasurement institute is NPL which istaking a leading role in establishinginternational key comparisons in physicalmetrology Within the field of chemicalmeasurement NPL has delegated much ofthe work to LGC Together scientists fromthese two laboratories represent the UK atthe CCQM Activities in this area form partof the current DTI VAM Programme animportant aspect of which has been workingwith the Analytical Methods Committee ofthe RSC to establish a UK laboratorynetwork linked to LGC and to theinternational activities8

Information about the current VAMprogramme can be found on the DTI (httpwwwdtigovuk) and VAM(httpwwwvamorguk) websites Generalinformation about metrology the text of the

MRA and details of key comparisons are available on the BIPM website(httpwwwbipmfr) We are seekingadditional reference laboratories to join theUK network as well as field laboratoriesinterested in helping to test the concept oftraceable measurements in routine use Ifyou are interested in helping have specificcomments or questions on applying theconcept of traceability to chemicalmeasurements or would like an overviewand bibliography of the work at LGC in thisarea I would be pleased to hear from you(mslgccouk)

REFERENCES

1 The Analytical Services Sector An

Analysis of Factors Contributing to

Sectoral Competitiveness Mike Sargent

and Reg Perry April 1996 (A report

prepared for the DTI Chemicals

Directorate by LGC)

2 lsquoThe Analytical Market Analytical

Science and Policyrsquo (1999 Annual

Review of the Government Chemist)

2ndash4 1999

3 lsquoDetection of adulteration of honey

application of continuous-flow IRMSrsquo

Helena Hernandez VAM Bulletin 18

12ndash14 Spring 1998

4 lsquoThe accurate analysis of trace metals in

clinical samples using ICP-MSrsquo Justine

Turner Ben Fairman and Chris

Harrington VAM Bulletin 20 12-16

Spring 1999

5 lsquoThe analysis of metal speciation using

LC-MSrsquo Chris Harrington VAM Bulletin

21 13ndash18 Autumn 1999

6 lsquoTraceabil ity and Uncertainty in

Chemical Analysisrsquo Mike Sargent VAM

Bulletin 17 11ndash12 Autumn 1997

7 lsquoHigh Accuracy Analysis of Inorganic

and Organic Analytes Using Isotope

Dilution Mass Spectrometry (IDMS)rsquo

Tim Catterick Ben Fairman Mike

Sargent and Ken Webb VAM Bulletin

17 13-15 Autumn1997

8 lsquoAchieving High Accuracy In Chemical

Analysisrsquo Mike Sargent VAM Bulletin

18 10ndash11 Spring 1998


E D I T O R I A L


G U E S T C O L U M N

Iain Ogdenand HughPenningtonUniversity of Aberdeen

The press has given such a high profileto food poisoning that the words

E coli have become synonymous with illnessand disease What they are really referring toof course are the pathogenic strains whichmicrobiologists call enterohaemorrhagic ndashE coli (EHEC) and more specifically in theUK and N America serotype O157 Here inthe UK we have the unenviable record of one of the worldrsquos worst outbreaks due to E coli O157 which affected 500 people across Central Scotland and resultedin 20 deaths1

But the ordinary E coli is a harmlessbacterium living in the gut of humans andother higher vertebrates Theodor Escherichfirst identified the organism in 1885 from thestools of breast fed infants and discoveredits ability to coagulate milk with acid and gasproduction This ability to ferment lactose isthe basis of differentiating E coli from otherclosely related bacteria and because of itsoccurrence in faecal material the presenceof E coli is used as indicator of poor hygienein food and food production Classicalbacteriologists use four additionalbiochemical tests to identify E coli theproduction of indole from tryptophan at theelevated temperature of 44degC the methylred reaction the Voges-Proskauer reactionand utilisation of citrate (IMViC) E colitypically gives a + + - - response in theIMViC tests To reduce both the time andcosts of such analyses identification usingjust the lactose and indole tests are now performed

The isolation identification andenumeration of E coli has therefore become

a common test in routine food testinglaboratories A wide range of proprietary kitshas made the analysis easier to perform andresults are available within two workingdays The majority are based onchromogenic or fluorogenic signals fromsingle biochemical reactions such as szlig-Dglucuronidase activity In addition rapidmethods incorporating techniques such aselectrical impedance flow cytometry ATPbioluminesence and membrane filtration canbe used to detect E coli and can also includesome degree of automation for testingmultiple samples

the words E coli have become synonymous with

illness and disease

The presence of E coli in foods mayindicate the presence of additionalpathogenic micro-organisms The realproblem occurs with the identification ofpathogenic E coli strains Not only are theyoften present in low numbers (lt100g) butthere is nearly always a high incidence ofcommensal E coli and other microfloraassociated with that particular food Theinfectious dose of E coli O157 is estimatedto be very low (lt10 viable cells) thusnecessitating sensitive detection techniquesFoods such as dairy products and cold meatshave short shelf-lives and have beenimplicated in E coli O157 outbreaks Rapiddetection methods are required by the foodindustry and regulatory authorities to helpensure that foods are not contaminated withthe organism prior to sale

There are two biochemical reactions thatdistinguish E coli from the serotype O157E coli O157 does not ferment sorbitol(strictly speaking it slowly metabolisessorbitol in 2-3 days) and it does not possessthe szlig-D glucuronidase enzyme Reactionsbased on these properties were initially usedto differentiate between the two groupsSorbitol replaced lactose in selective E colimedia (eg MacConkey agar) and thosecolonies with no acid reaction were further

screened by serology to determine thepresence of E coli O157 This method hasserious drawbacks in the lack of sensitivityThe analysis of faecal and food samplesproduced plates with large numbers ofsorbitol fermenting colonies masking anynon-sorbitol fermenting E coli O157 Onesolution to this was to use DNA techniquesto recognise EHEC within a sweep of allcolonies on such a plate PCR methods orlabelled probes could target one or both ofthe verotoxin genes possessed by E coliO157 but these technically difficultmethods requiring relatively expensiveequipment have never been popular withthe routine testing laboratory

The advent of immunomagneticseparation (IMS)2 brought E coli O157analysis to within the capabilities of alltesting laboratories although there is nowthe additional restriction of category IIIfacilities for final confirmation By coatingpolymer or ceramic beads with antibodiesagainst surface antigens we have a way of specifically attracting target bacteriarequired for further analysis If the beadshave magnetite cores then they can beeffectively recovered using a magnet Thetechnique is commercially availabletechnically simple to perform and costsapproximately pound3 per test Appropriateequipment costs ltpound1000 The volume of immunomagnetic beads used per test is 002ml which contains gt106 beads Aliquotsof 1ml are assayed from food samplesenriched in semi-selective media Samplesare placed in a rack mixed for 30 minutesbefore discarding the supernatant and re-suspending the beads (without the magnet)in wash buffer Two further washing stagesare performed prior to transferring the beadsto a selective agar After overnightincubation presumptive colonies areconfirmed with latex agglutination antiseraResults are available within 24 hours

A wide range of IMS protocols havebeen investigated This laboratory hasrecently completed a study comparingchemical composition and incubation

Methods for testing Escherichia coli


temperatures of enrichment broths and theselective agars used in the IMS procedureArtificially inoculated E coli O157 in arange of foods were tested and methodsvalidated on samples containing naturallyoccurring E coli O157 To show methodsensitivity under extreme circumstances thespiked studies used low numbers (lt1g) ofphysiologically stressed target bacteria in the presence of high numbers ofundamaged background micro-organismsFoods of known association with E coliO157 were studied minced (ground) beefwas tested initially with subsequentvalidations performed on cheese apple juiceand pepperoni A summary of the results isshown in Table 1 All tests were performedusing cocktails of 4 or 5 strains of E coliO157 to minimise the effect of singleatypical strains To physiologically stress E coli O157 the cocktail wasi) inoculated into mince and subjected to

a series of freezethaw cycles added tofresh mince (containing high numbers ofnon-E coli O157) and tested as indicated

ii) inoculated into a high salt (135 wv)low pH (49) low temperature (5degC)broth and spread on the surface ofpepperoni samples

iii) inoculated into apple juice and stored at 4degC for ten days prior to transferringto apple juice for testing

iv) surface spread onto cheese and stored at 4degC before testing Results show quite clearly the beneficial

effect of elevated temperature which appearsto inhibit competing microflora The use of

cefixime and cefsulodin is widespread inIMS enrichments (brotha) but at thereduced concentration of 25 (brothd) theyappeared to have little effect and recovery ofE coli O157 was similar to brothb Someantimcrobials used in these techniques canbe inhibitory to E coli O1573 (MacRae et al1997) and therefore they should be usedwith caution The International Organisationfor Standardisation4 favour mTSB+N at42degC but in this comparison it was lessefficient than BPW-V pH 70

Selective agars chosen for comparisonincluded several based on sorbitolMacConkey The selective additions ofcefixime and potassium tellurite favour Ecoli O157 isolation This medium has thedisadvantage of being unable to distinguishsorbitol fermenting E coli O157 fromcommensal E coli which are uncommon inthe UK but found regularly in otherEuropean countries Commercially availablechromogenic agars based on alternativebiochemical reactions were included whichwould also support the growth of E coliO157 strains inhibited by cefixime andtellurite Incubations were at 37degC exceptfor SD-39 which was at 42degC The resultsare presented in Table 2

The results indicate the superiority of Rainbow agar which showed very little growth from non-target bacteriamaking recognition of E coli O157 easyUnfortunately it is rather expensive forroutine use and therefore for economicalreasons this laboratory plates the immuno-beads equally onto CTSMAC (agarg) and

Chromagar (agark) which performed well asindicated in Table 2

Validation of methods was done on twofoods with naturally occurring E coli O157which were available in reasonably largeamounts during the course of this studyLevels of target bacteria were found to below (data not shown) but their physiologicalstatus was unknown Three enrichmentbroths were comparedi) BPW-VCC 37degC used in original

IMS protocolsii) mTSB-N 42degC the ISO enrichment brothiii) BPW-V 42degC optimum as shown

in Table 1The results indicated the superiority of

BPW-V incubated at 42degC The other twoenrichments tested failed to recover E coliO157 in replicate tests which might indicatethe presence of sub-lethally damaged cells inthe foods tested Beads were plated ontoCTSMAC and Chromagar

In the light of these results thislaboratory routinely screens foods for E coliO157 by enriching in BPW-V at 42degC andplating the beads onto CTSMAC andChromagar incubated at 37degC It is worthnoting that this method showed greaterrecoveries of target cells than the proposedISO method

E coli O157 is by far the most common


Enrichment medium 37degC 40degC 42degC

BPW-VCCa poor poor good

BPW-V pH 70b poor very good excellent

BPW-V pH 60c poor NT good

BPW-V + 14 C+Cd poor very good excellent

mTSB+Ne poor good very good

EC medium + Nf poor NT good

a BPW + vancomycin (8 mgl) + cefixime (005 mgl) + cefsulodin (10 mgl) b Buffered peptone water (BPW) + vancomycin (8 mgl) pH 70c BPW + vancomycin (8 mgl) pH 60d BPW + vancomycin (8 mgl) + cefixime (00125 mgl) + cefsulodin (25 mgl) e Tryptone soya broth + bile salts (15 gl) + novobiocin (20 mgl)f EC medium + novobiocin (20 mgl)

NT ndash Not tested

Table 1 Recovery of E coli O157 from food by different IMSenrichment treatments at different temperatures

g Cefixime tellurite sorbitol MacConkeycefixime 005 mgl potassium tellurite25 mgl

h Sorbitol MacConkeyi Sorbitol MacConkey + cefixime and

tellurite at one third normal strengthj Sorbitol MacConkey + cefixime and

tellurite at two thirds normal strengthk CHROMagarTM O157 isolation mediuml Quality Life Sciences E coli O157

isolation mediumm Biolog RainbowTM E coli O157

isolation medium

ndash Indicates zero recovery

Selective agar Rating

CTSMACg very good

SMACh poor

SMAC + 13 CTi poor

SMAC + 23 CTj poor

CHROMagarTMk very good

SD-39l ndash

RainbowTMm excellent

Table 2 Comparison of E coliO157 selective agars



EHEC isolated in the UK but this is not thecase elsewhere in the world Serotypes O26O111 O103 and O145 are regularly isolatedin other countries and have been listed byWHO as amongst the lsquotop fiversquo CommercialIMS systems are available only for serotype

O157 and while it is relatively easy to labelbeads with antibodies to any EHEC theprotocols for optimum isolation remainunknown at this time This highlights theneed for continued research in this area offood microbiology

REFERENCES

1 Pennington T H The Pennington Group

Report on the circumstances leading to

the 1996 outbreak of infection with E

coli O157 in Central Scotland the

implications for food safety and the

lessons to be learned Edinburgh The

Stationery Office UK 1997

2 Chapman P A Wright D J and Siddons

C A A comparison of immunomagnetic

separation and direct culture for

the isolation of verocytotoxin ndash

producing Escherichia coli O157 from

bovine faeces J Med Microbiol 40

424ndash427 1994

3 MacRae M Rebate T Johnston M and

Ogden I D The sensitivity of Escherichia

coli O157 to some antimicrobials by

conventional and conductance assays

L Appl Microbiol 25 135ndash137 1997

4 Anonymous Draft International

Standard 16654 Microbiology of food

and animal feeding stuffs ndash Horizontal

method for the detection of Escherichia

coli O157 British Standards Institute

London 1999

Philip Slackand PeterFarnell LGC

Introduction

The Quantitative Ingredients DeclarationAmendment12 is one of the most

radical amendments to the part of the FoodLabelling Regulations3 (covering the bulkcomposition of foods) since the FoodLabelling Regulations of 1984 Apart from

foods to which specific compositionalrequirements apply food law up to now onlyrequired ingredients to be listed on the label Where no specific compositionalrequirements apply the Regulationsprescribe the format for the nutritionallabelling of foodstuffs so that foodmanufacturers could voluntarily declare food macro-components of nutritionalsignificance such as meat and fat contentSince 14 February 2000 labelling of foodproducts must now include a QuantitativeIngredients Declaration (QUID) TheRegulations also cover the supply of food to restaurants and other caterers as well

as for retail sale Measurement issues relating to the

nutritional labelling of foodstuffs are wellunderstood as voluntary declarations dependupon chemical analysis of the finishedfoodstuff Apart from the requirement fornutritional declarations the determination ofmeat (via total nitrogen) fat carbohydrateand moisture contents for example havetraditionally been an important part of thequality control of food manufacturingHowever the emphasis in food manu-facturing has been moving away from qualitycontrol towards quality assurance by bettercontrol of ingredients and processes This

F O C U S O N S E C T O R S

VAM and the measurementissues related to QUID



spirit is seen in the QUID amendment inthat declarations of ingredients must for themost part be based upon the weight of theingredient added in the recipe at the so-called lsquomixing-bowlrsquo stage This is perhapsthe first challenge to be addressed since inmany manufacturing processes the lsquomixing-bowlrsquo is more of a concept than a realitywith ingredients sometimes being addedthroughout the process for example saucesto the final packaged product

The VAM principles and QUID

The six VAM principles are listed insidethe front cover of this Bulletin and are aninstrument of the UK National Measure-ment System These principles weredesigned for chemical testing laboratoriesand their relationship with testing thereforebeing well understood When testing foodproducts to determine the concentration of volatile ingredients eg alcohol testlaboratories will need to have the VAMprinciples firmly in mind since these aredesigned for such activities One easy way toensure this is to use a test laboratory that isaccredited by UKAS specifically for this teston a defined food matrix or otherwise toISO Guide 25 or EN 45001 Alternativelythe laboratory should be audited by acompetent person to ensure that it isfulfilling the requirements of the VAMprinciples This article examines howapplicable the spirit of the VAM principlesare to the wider measurement issues posedby QUID It explores the relationshipbetween the VAM principles and the lsquomixingbowlrsquo examines them in relation to theinterpretation of data then considers theenforcement of the QUID Directive

Measurement for a QUID ndashDo you measure-up

1 The lsquomixing-bowlrsquoManufacturers need a system of

accurately measuring and recording theweights of ingredients added at any stage ofthe process as well as enabling them tocompensate for processing losses They willneed such records not only for their ownquality assurance requirements but also as ameans of supporting a declaration given on aparticular unit of a product at point-of-saleImplicit in this is the need for consistentand traceable measurements of weight and a

meticulous system of recording such dataThey will need to determine the content ofcertain volatile ingredients in the finishedproduct analytically It can therefore beargued that many of the VAM principlesform a good basis for judging themeasurement challenges with respect to thelsquomixing-bowlrsquo ingredients It is interestingtherefore to consider how these principlesmight relate to QUID

The first VAM principle relates to thepurpose for which the measurement isneeded It is important to decide howprecise the measurement needs to be andwhether the measurements being made areaccurate enough or perhaps already moreaccurate and precise than is necessary Anoperative weighing large amounts of aningredient eg meat will find it easier tomake accurate additions to a bulk than whensmall amounts of say an additive inconcentrated form is put in This is easier todispense accurately if an additive is supplieddispersed in a lsquobulking agentrsquo Suchspecifications will depend on the situationand need to be agreed in advance This willbe imperative in deciding whether the

measurement instruments eg weighingmachine already in place are appropriate

The second principle involves assessingmeasurement instruments against this agreedspecification The precision of an analyticalbalance will obviously not be required forweighing meat However all instrumentshave their own range of uncertainty ofmeasurement and this must not approach orexceed the overall precision required in theagreed specification Accuracy anduncertainty are both determined throughcalibration and it is therefore important todetermine whether appropriate calibration isbeing carried out

To address the third principle it isimportant that operatives understand theabove mentioned requirements and havebeen properly trained in the use of theinstruments Routine checks of theircontinuing competence should ideally bemade through the weighing of check batchesof already known weight

The fourth principle is best tackled byan internal audit by a Quality DepartmentOperatives should be observed carrying outthese operations at defined regular intervals



The traditional calculation of meatcontent is based upon the determination oftotal nitrogen content multiplied by anapproved constant Corrections are thenmade for other nitrogen containingcomponents eg collagen soya proteinmilk protein excess connective tissueSome fat can then be added in for the calculation of total meat QUIDdeclarations from the lsquomixing bowlrsquo willalmost certainly differ from those arisingfrom calculations made in this way fromanalytical data by virtue of the fact thatMember States of the European Unionhave different definitions of meat (there isalso another mechanism by which thisdisparity might occur involving nutritionaldeclarations of protein ndash see below) Suchdefinitions range from all striated muscle inGermany predominantly muscle and somefat in the UK to considerable inclusions ofoffal in some other Member States SomeMember States do not define meat at allThus the raw ingredient will vary inquality and chemical composition Thevariable water content of fresh meat willalso be an issue here as will be its nitrogenfactor It would seem to be of greatimportance that QUID declarations formeat content are harmonised across the EU

The harmonisation of QUIDdeclarations for meat may depend on aconsistent definition of meat as aningredient The European Union hasproduced its own definition but so farMember States have been unable to agreeto this Various national regulationscurrently allow manufacturers tolsquoconstructrsquo a lsquomeatrsquo content by the additionof different parts of the carcass which mayinclude Mechanically Recovered Meat(MRM) The extent to which this canhappen will therefore vary greatly from oneMember State to another How this willaffect the movement of products betweenMember States of the EU is unclear sincethe issue of how to lsquoQUIDrsquo products forexport remains to be properly resolved Itwould appear that products with QUIDdeclarations made at point-of-productionin accordance with the NationalRegulations defining meat must beaccepted in all Member States This has

the potential to confuse the customerattempting to make comparisons betweendifferent products at point-of-sale orindeed at home after purchase

Declared percentage meat content willtherefore reflect differing ingredientsranging from pure muscle or lean meat atone extreme to a mixture of other parts ofthe carcass including fat skin and rindThere is also some feeling that rather thanhaving an EU wide legal definition of meatthere should be a requirement forpercentages of individual cuts of meat orother parts of the carcass to be declaredConsumers would know exactly what theyare eating and how this relates to theirown perception about what meat is Thiswould also help them to make a priceversus quality assessment of the productenabling manufacturers to produce lsquoup- ordown-marketrsquo products to suit the varyinglsquovalue for moneyrsquo perceptions In somecases this approach would require theabolition of Compositional RegulationsWhichever approach is taken a keyelement of this debate centres aroundwhether better analytical methods shouldbe developed for detecting and quantifyingthese different types of lsquomeatrsquo allowingverification of the ingredients used inmanufacture Certainly lsquoconstructedrsquo meatcontents might only be verified analytically

Normally QUID declarations will befor a typical quantity of an ingredientrounded to the nearest whole numberreflecting the producerrsquos normalmanufacturing variations in accordancewith good manufacturing practice Anexception to this is where the labellingplaces special emphasis on an ingredient incases where the food is alreadycharacterised by the presence of thatingredient Here a minimum content mustbe declared which might be legallyprescribed if a Compositional Regulationapplies An example might be where thepork is particularly emphasised in cannedlsquopork sausagersquo Conversely if the labellingemphasises a low level of an ingredientthen a declaration of maximum contentmust be given An example here might be ifthe low level of fat is emphasised in a spread

Continued on page 10

The meat content challengeCalibration and traceability of

measurement are also about ensuring that aweight of x kilogrammes represents the sameamount of ingredient as it does in anotherfactory down the road It will if the fifthVAM principle is adhered to

Finally the sixth VAM principlerequires quality assurance and qualitycontrol procedures In this context qualityassurance involves having appropriatewritten standard operating procedures andproper records of calibration and weighingsof ingredients to prove that all actions werewithin specifications

2 Interpretation of information from measurementAnother possible application of the

VAM principles is in the conversion of testdata into useful information Perhaps one ofthe biggest consequences of QUID is that inaddressing the quantitative issues relating tofood ingredients declarations it also raisesthe issue of the quality of ingredients andtheir impact in the interpretation of testdata Since ingredients of varying quality willalso differ in their composition someconcern has been expressed bymanufacturers about whether lsquolike will becompared with likersquo when consumerscompare different products with identicalQUID declarations Another way that thismight also become apparent as an anomalyto the consumer is that it is also feasible that two otherwise identical products with the same QUID declarations mighthave significantly different nutritionaldeclarations and vice versa

Nowhere is this more apparent than in theissue of meat content where very specificmeasurement issues are raised Here therequirement is to measure the level of ananalyte and convert this into a value for meatcontent This is an interpretative step that alsorequires a database from which appropriateconversion factors can be established andused By way of example we have examinedthe meat content issue in more detail (seeldquoThe Meat Challengerdquo [right])

VAMWhat does all this have to do with the six

VAM principles The connection comes viathe fact that in all situations whereinterpretation of data is required to ascertaincompositional information or the level of aningredient an lsquoanalyteingredientrsquo relation-ship is required that can be likened to asecondary calibration graph This is thelsquographrsquo that can be drawn showing therelationship between the level of the chosenanalyte and the componentingredient of interest which is to be quantified (seeFigure 1) The slope of this lsquographrsquo willdiffer for the individual cuts of meatdifferent parts of the carcass and for MRMfor example Appropriate corrections tovalues read from the lsquographrsquo need to bemade for collagen content because of itscontribution to the measured value for totalnitrogen Also the relationship between thevalues read from the lsquographrsquo and the weightof meat added to the mixing-bowl will needa level of understanding to allow a sensibleinterpretation to be made These issuesraised for meat are also similarly evident forother areas of food analysis such as fruitjuice content or milk content They indicatehow difficult it is for food analysts to drawthis lsquographrsquo with respect to the range offactors that need to be taken into account

Interpretative skills cannot currently becovered within the scope of accreditation by

UKAS because accreditation currentlyrelates to the making of a test measurementnot to the interpretation of the measurementresult It is now being argued that theyshould be given the economic importance ofthe opinions being expressed daily bylaboratories on test reports The adoption ofISO 17025 will in future allow the reportingof opinions and interpretations to beaccredited This means that all aspects of theQuality System will need to be extended tocover interpretative skills These will includestandard operating procedures methodprotocols the databases and relationshipsbetween test data and an interpretationbeing given by that laboratory staffexperience qualifications and trainingrecords etc Many laboratories may not beaware of these forthcoming changes or of theimplications to their quality systemsTherefore an extension of the VAMprinciples to include the interpretation oftest data would assist laboratories with theirpreparations for the accreditation of services requiring the provision of opinionsin test reports

How might this be done

The first VAM principle might

encourage us to ascertain whether the need

is to interpret test data to confirm a QUID

or establish the relationship between this

declaration and a nutritional declaration or a

compositional requirement

1 0 V A M B U L L E T I N


Relationship between the predicted level of marker analyte and ingredient concentration L = level of analyte found Ldl = maximum level of analyte found in the ingredient DL = detection limit of ingredient L = level of analyte found Imin= minimum level of ingredient Imax= maximum level of ingredient A = average content of ingredient

Figure 1

Continued from page 9This complex situation is com-

pounded by another requirement thatdeclarations calculated by weight fromthe recipe at the mixing-bowl stage mustnot have included in the calculation anywater or volatile ingredients lost duringprocessing It is interesting to considerthe complications that could thus arisewith the meat content declaration

Water losses during processing canbe extremely variable Additionallyseparating fat which is often skimmedoff might not take place to a consistentdegree Here then is the othermechanism by which an anomalybetween a nutritional declaration and aQUID will occur This is the issue ofhow for example the protein content ina finished product will relate to a meatQUID The departure from theestablished practice of relating meatcontent to the nitrogen content of rawmeat for the purpose of labellingdeclarations will mean that differentproducts with the same QUID for say ameat ingredient may have substantiallydifferent protein declarations even whenthere is obviously no other source ofprotein present There is potential herealso to confuse the consumer who maywonder how the meat from onemanufacturer is giving him more or lessprotein than the meat from another Inthe short term manufacturers canpresumably avoid this issue by omittingnutritional labelling from their packagingThe whole issue will however need to beresolved if the UKrsquos suggestion to theEuropean Union to make nutritionallabelling compulsory goes ahead Thiswill provide a challenge for theenforcement authorities who areresponsible for enforcing both parts ofthe legislation and will presumably stillneed to relate analytically derived proteinand calculated meat contents to theQUID for meat It is likely that thereconciliation of these values will requiremuch input from analytical chemists

For the second VAM principle one

needs to ask if the databases available as

well as the methods for using this data to

prepare the lsquoanalyteingredientrsquo relationship

are fit-for-purpose Have these been properly

tested MAFF (the UK Ministry of

Agriculture Fisheries and Food) have been

trying to address this issue by funding

research work under the auspices of the

RSC Analytical Methods Committee on the

composition of red meat chicken and

scampi but more information on the

composition of other raw materials such as

turkey meat and salmon is needed In 1998

proposals were invited to conduct

collaborative studies to achieve this involving

financial support partly from MAFF and

from industry Similarly in 1999 proposals

were called for to determine the composition

of commercially important fish species

MAFF clearly see a need for these data to

enable analytical checks to be made on the

content of meat or fish in final products in

order to implement QUID This differs from

another view sometimes expressed that

factory inspection alone would be sufficient

for enforcement purposes (see below)

MAFF has also been trying to address

the fitness-for-purpose issue with respect to

other interpretative issues Last year it

called for the development of analytical

methods for the determination of plant-

based ingredients with respect to the

implementation of QUID As with meat-

based products implementation of QUID

might be difficult in the many cases where a

legal definition for a plant-based product

does not exist Analytical chemists may well

be involved in the process of establishing

such legal definitions as well as in developing

methods for the determination of these

ingredients The establishment of legal

definitions for food ingredients is however a

contentious issue for some sectors of the

food industry especially the meat sector

Are the staff interpreting analytical data

qualified and competent for this task as is

required by the third VAM principle A

member of staff might be highly competent

at all the technical aspects of making a test

measurement This does not necessarily

mean that they understand the underlying

scientific issues sufficiently to form an

opinion about those test data It is evident

that generally more highly qualified and

experienced scientific staff will be required

to interpret data and give the customer an

opinion It is likely that most customers

would expect this The fourth VAM principle might require

laboratory audits and assessments foraccreditation to add interpretative skills tothose of the measurement of an analyte Thismight require a substantial extension oflaboratory audit and review protocolsbefitting the much more specialist functionof the laboratory justified by the addedfinancial value that providing such servicespresumably brings to that laboratory

It is clear that measurements of meat

content in one location in Europe cannot be

consistent with those made elsewhere since

Europe has not yet agreed a legal definition

for meat The fifth VAM principle would

require laboratories across Europe to be

preparing their lsquoAuthenticity Calibration

Relationshiprsquo in the same way Obviously

they cannot be doing this

Finally it is unlikely in many cases that

well defined quality control and quality

assurance procedures will exist for the

interpretation of test data as would be

required by the sixth VAM principle

Accreditation by UKAS does not currently

extend beyond the measurement of

the analyte

Perhaps VAM should now raise

this standard

Enforcement of QUID

Do we need testing to enforce QUIDand are the VAM principles relevant FoodLaw applies to products at point-of-saleThis means that enforcement will relate to aparticular unit taken from a retail outlet by aTrading Standards Officer One obviousmeans of enforcement is to test the sampleif an appropriate test exists The majordrawback to this approach is that analyticalchemists do not always have an appropriatetest that they can use If this approach istaken the sample is divided into threeportions one is sent to a public analyst andone can be analysed by a test laboratoryappointed by the lsquoownersrsquo of the sample Incases of dispute LGC is often required toanalyse the third portion in its role as theofficial UK referee laboratory under theprovisions of the Food Safety Act 1990

Trading Standards Officers also havethe powers they need to enter factories toenforce Food Law They would need torelate their observations in the factory to aunit of product previously purchased from aretailer This means that they would not onlyneed to audit the manufacturing process butwould also need to examine productionrecords relating to the batch from which thatunit of product originated in order to ensureproper lsquocalibrationrsquo

The first issue that arises concernsenforcement of imported productsObviously Trading Standards Officers willnot normally be able to inspect overseasproducers This approach would rely upon asystem of networking with similarenforcement bodies in other states Recentexperiences have shown that enforcement by this route can be a long-winded process Secondly factory inspection is a time-consuming process and it is debatableas to whether or not local authorities havethe resources to do this effectively In bothcases it would be easier if the informationcould be gained by testing the end productas is done for enforcement of nutritionallabelling declarations

Herein lies the measurement challenge tothe analytical chemistry profession Todevelop appropriate tests through technologytransfer and innovation then to validate themin a manner that includes the interpretativestages required to deliver an opinion to thecompetent authority All this must be inaccordance with the appropriate VAMprinciples so ensuring fitness-for-purposeFinally to ensure that everyone irrespectiveof geographical location is applying theseprocedures in such a manner as to achieveequivalent data and its interpretation

REFERENCES

1 Directive 974EC (1997) lsquoOn the

approximation of the laws of the

Member States relating to the labelling

presentation and advertising of

foodstuffsrsquo Official Journal of the

European Communities L43 21ndash23

2 The Food Labell ing (Amendment)

Regulations 1998 SI 19981398

3 The Food Labelling Regulations 1996

SI 19961499




Ken Webb andMike SargentLGC

Mass spectrometry is widely regarded asthe technique of choice for an

extensive range of demanding analyticalmeasurement applications because it offers apowerful combination of accuracysensitivity specificity versatility and speedIt is frequently used for both theidentification and quantitation of traceimpurities an application of particularimportance to regulatory or forensicapplications Indeed mass spectrometry israpidly becoming the preferred detectionsystem for many gas or liquid chromat-ographic separations used in these fieldsbecause of its perceived capability to provideunequivocal identification of the targetanalyte In addition it is widely believed thatsimpler or more rapid chromatographicseparations can suffice due to the greaterpower of a mass spectrometric detector in ensuring that the signal monitoredoriginates from the analyte and not aninterfering species

The routine identification andmeasurement of compounds using massspectrometry can however lead toconflicting requirements particularly whereadditional compromises are made in theinterest of speed and economyIdentification is normally achieved bymonitoring a number of structurallysignificant ions of a compound whereas forsensitivity purposes accurate quantitation isoften carried out by monitoring only oneion Consequently there can be a number ofdifferent ways of carrying out identificationand quantitation ranging from full scans tomonitoring a single ion A satisfactorybalance must be achieved between thenumber of ions monitored and optimumsensitivity Moreover it is essential that theactual ions chosen for monitoring are

selected with a knowledge of potentialproblems which may arise For example thesame ion could result from fragmentation ofanother possibly similar compound or thesignal may overlap that from a different iondue to inadequate mass resolution of thespectrometer In many cases the optimumchoice of ion for certainty of identificationwill require expert knowledge of massspectrometry the characteristics of theseparation techniques and the chemistry ofthe analyte and sample This expertise is notalways available particularly in routinescreening applications and concern has arisen regarding the consequences ofmis-identification particularly where legalaction may be taken on the basis of theanalytical result

Official guidelines or criteria

As a result of this concern severalorganisations have produced guidelines orcriteria for selection of ions to be monitoredin critical applications One example isconfirmation of residues of growthpromoting agents illegally used in thefattening of cattle12 within the EuropeanUnion (EU) The EU criteria2 state that fourions should be measured the intensity ofwhich should deviate by no more than plusmn10in electron ionisation (EI) mode from acorresponding standard It is interesting tonote that for use as a screening methodsingle ion monitoring of the most abundantdiagnostic ion is specified The requirementto monitor four ions for the confirmation ofidentity may seem somewhat rigorousparticularly as these criteria are based onlsquoexpert opinionrsquo rather than on evaluation ofanalytical data from confirmatory analysis1It has been found in practice that thesecriteria are proving difficult to meet forseveral analytes especially where some ofthe diagnostic ions are of low mass orrelatively low intensity3 The consequence ofthis is that a relatively high number of falsenegative results could be obtained in theroutine inspection for the abuse of growthpromoters Ideally the number of false

negative results should be minimal howeverwith the EU criteria of four diagnostic ionsthis is not believed to be the case3Consequently work is currently underway3with the aim of providing a statisticallyfounded strategy to determine the criteriaapplicable to mass spectrometric data so asto achieve optimisation of false positive andfalse negative results in these analyses

Systematic studies of ion-monitoring criteria

The above example highlights the need

for and lack of systematic studies of the

number of ions which should be monitored

to confirm identity4 One of the few

published examples5 was the investigation of

the number of ions (in EI mode) that must

be monitored to produce an unambiguous

identification of a given compound In this

study an estimate was made of the minimum

number of ions it was necessary to monitor

so as to produce an unambiguous

identification of diethylstilboestrol (DES)

using low resolution mass spectrometry

DES is an ideal compound for such a study

since it exhibits an abundant molecular ion

and has a number of structurally significant

fragment ions Using a database of 30000

spectra it was found that searching the

database for three ions all with appropriate

intensity limits produced only one match

DES It was considered that a realistic

relative intensity variation for the ions

monitored based on a standard EI

spectrum would be plusmn5 although this was

recognised as being flexible If additional

specificity is present such as GC retention

time then the intensity variation could be

expanded beyond these limitsIt was recommended5 that for

identification purposes three or morecharacteristic ions should be monitored tobe present within an acceptable ratio Thisstudy5 was published in 1978 and a modernversion of this approach using an updatedmass spectral library (of unknown origin)containing some 270000 spectra was

C O N T R I B U T E D A R T I C L E S

The reliability of mass spec foridentification purposes



published in 1997 by the same author6 Theresult again showed that three characteristicions with reasonably tight specifications forrelative intensities are required to uniquelyselect DES from the larger database

An extended systematic study7 of anumber of compounds of analytical interestwas carried out at LGC in 1998 as part ofthe VAM programme using similar criteriato those in the 1997 study The compoundswere chosen to be representative of theforensic and agro-chemical fields whereproper identification is particularlyimportant Results for one of thecompounds malathion (an organo-phosphorous pesticide) are shown in Table1 This table shows the monitoring of up tothree characteristic ions of malathion (molwt 330) In addition the relative intensitiesof the ions monitored are also taken intoaccount This is done by setting an lsquointensitywindowrsquo for each ion based on the ionintensities from a reference spectrum plus orminus 20 Table 1 also shows exampleswhere the relative intensities are not takeninto account (ie window is 1-100) As theidentification criteria are made morestringent the number of matches decreasesquickly to the point where threecharacteristic ions with the correct relativeintensities (within plusmn20) uniquely identifiesmalathion The results of this extended studysupport those of the previous work on DES56

and show that monitoring three characteristicions of a compound with appropriate relativeintensity specifications is sufficient touniquely select the given compound from acomprehensive mass spectral library Thisnew study highlighted the importance thatthe chosen ions include the molecular ionand that moderately specific ion intensityranges are used

The lsquo3-ion criterionrsquo formolecular identification

Work such as that outlined above led tothe establishment of the lsquo3-ion criterionrsquo forelectron impact spectra568 In addition to thepresence of three characteristic ions thecriteria also specify that the relative intensitiesof the ions are within plusmn10 of the ratiosobserved from a standard If additionalspecificity is present such as achromatographic retention time then theintensity variation could be expanded beyondthese limits The 3 ion criterion is the onlybroadly recognised standard for unambiguousanalyte identification8 for all types ofionisation Although alternatives have beenproposed no other standard is so universallyrecognised as the best means of minimisingthe risk of a false-positive identification8

Current VAMrecommendations

Suggested identification criteria when

using GC-MS and LC-MS are given

below and are based on the 3-ion criteria

described above

1 The criterion of chromatographic

retention time should be used in

conjunction with mass spectral criteria

for confirmation of identity In general

the retention time of an analyte should

be within plusmn2 of a reference standard

2 Under conditions of electron ionisation

at low mass spectral resolution at least

three characteristic diagnostic ions

should be present one of which should

preferably be the molecular ion The

relative intensity of these diagnostic ions

should match those of a reference

standard to within a margin of plusmn20

3 When using chemical ionisation theguideline as at 2 should be followed butwith an acceptable margin on ionintensity ratios of plusmn25

Tandem mass spectrometrycriteria

In the case of tandem mass spectrometry(MS-MS) linked to a chromatographicsystem MS-MS itself confers considerablespecificity in compound identification It hasbeen suggested6 in this case thatconfirmation of identity requires observationof a precursor ion representing the intactmolecule (or a closely related fragment)plus one structurally significant product ionobserved at the same chromatographicretention time However in view of theincreasing use of chromatography-MS-MSto shorten clean up and analysis times manyinterferences could be present in sampleextracts It is likely that these may not beresolved from the analyte of interest Underthese circumstances when detection is byMS-MS it would be prudent forconfirmation of identity to be based onobservation of two structurally relatedproduct ions from one precursor ion (ideallythe molecular ion)

Relaxation of criteria

There are also circumstances where it isconsidered that the 3-ion criteria could berelaxed Such circumstances could includethe case where the matrix to be analysed hasbeen well characterised in the past and theprocedure is used for rapid pre-screening ofa large number of samples Another case isthat of dosing experiments using a specificcompound where it is clear that the compoundwill be present The determination of

Masses monitored

Mass Intensity Mass Intensity Mass Intensity No of matchingrange () range () range () compounds

330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1

Table 1 Results from spectral library matching study on malathion7


lysergide (LSD) in urine by LC-MS9

illustrates this point Normally for forensicpurposes three ions are monitored toinclude the (M+H)+ ion at mz 324 and thecharacteristic fragment ions at mz 223 and197 If LSD is known to be present throughdosing experiments then monitoring twoions to include the (M+H)+ ion at mz 324and the mz 223 ion is sufficient forestablishing its presence In this particularcase monitoring only two ions would alsobring about a considerable increase insensitivity of the procedure The limit ofquantitation (LOQ) of this procedure whenmonitoring three ions is 05 ngml As canbe seen from Figure 1 the 197 daltons ion ofLSD has only a 10ndash15 intensity relative tothe base peak Consequently if only twoions were monitored (mz 223 and 324) thelimit of detection would be improved by afactor of five to 01 ngml (the mz 223 ionhas an intensity relative to the base peak ofsome five times that of the mz 197 ion)Hence adopting this approach would bebeneficial particularly if measurements werebeing carried out at or near the LOQ

Conclusions

Clearly no single set of criteria canencompass all eventualities Considerationmust be given to fitness for purpose and ascientific judgement based on analyticalrequirements must be made However inorder for scientific data to be acceptablebetween organisations some form ofharmonisation is necessary Ideally thiswould incorporate the results of a systematicintercomparison utilising perhaps compoundsof a similar nature and a suitable databaseThis article is an attempt to set the scene for

further discussion of an important subject

REFERENCES

1 De Ruig W G Stephany R W and

Dijkstra G J Assoc Off Anal Chem

72487ndash490 1989

2 EEC directive 93256 No L 11864

(1993)

3 Van Rhijn H A and Van de Voet H

Advances Mass Spectrom 14 CD

ROM ndash WeOr09 1998 (Abstract only)

4 Burlingame A L Boyd R K and Gaskell

S J Anal Chem 70 647Rndash716R 1998

5 Sphon J A J Assoc Off Anal Chem

61 1247ndash1252 1978

6 Baldwin R Bethem R A Boyd R K

Budde W L Cairns T Gibbons R D

Henion J D Kaiser M A Lewis D L

Matusik J E Sphon J A Stephany R

and Trubey R K J Am Soc Mass

Spectrom 8 1180ndash1190 1997

7 VAM Report LGCVAM1998010

Optimisation of the number of ions

which are acceptable for identifying

different chemical species using

GC-MS (1998)

8 Bethem R A and Boyd R K J Am Soc

Mass Spectrom 9 643ndash648 1998

9 White S A Kidd A S and Webb K S J

Forensic Sci 44 375ndash3791999


Figure 1 Electrospray mass spectrum and structure of LSD

David Booker

AEA Technology

Environment

Trends in air quality legislation

Three independent scientific committeeswithin the UK have published reports123

indicating concern over the health effects ofparticle exposure These concerns have givenrise to a debate on the need for additional

legislation to further reduce particulateemission levels One of these committees1

concluded that it would be imprudent toignore a probable causal link betweenparticulate exposure and acute (and chronic)health effects However this statement isqualified by the recognition that there is a

Ultrafine particles and air quality control


degree of uncertainty over the role of veryfine particles (less than 1 microm aerodynamicdiameter) The UK Expert Panel on AirQuality Standards (EPAQS) of thelsquoDepartment of the Environment Transportand the Regionsrsquo has recommended3 that the24 hour exposure limit be reduced from thecurrent 150 microgm3 to 50 microgm3 (presentannual limit based on the current USEPA(US Environmental Protection Agency)guidelines) In addition the reportrecommends that efforts be made to furtherreduce the 50 microgm3 limit year on year andthat the number of days where the limit isexceeded are reduced year on year This isconsistent with the approach adopted by theCommission with respect to the EU AirQuality Framework Directive

The USEPA has issued a discussiondocument with respect to particles andhealth suggesting that further sizediscrimination is required within PM10sampling Ambient particulate is morehomogeneous across continental US andtherefore a dual PM25 and coarse material(CM PM10 ndash PM25) standard has been putforward to the USEPA as a staff paper It isanticipated that annual primary standards of50 microgm3 for PM10 and 15 microgm3 for PM25

will be submittedIn conclusion there is a body of

evidence to suggest that future emissionslegislation within Europe and the US willinclude a reduction in particulate emissionlevels coupled with a degree of sizediscrimination Number concentration limitsmay also be adopted in Europe dependingon the outcome of new researchprogrammes The likely time scale forintroduction of these changes is 5ndash8 yearsincorporating a window for further research

Implications for vehicleemission regulations

The setting of vehicle emissionregulations is a complex and iterativeprocess which has to take account of theevolving understanding ofbull health and environmental motivations

for changes in air quality legislationbull timing of the introduction of changes

in air quality legislationbull understanding of the contributions of

vehicle emissions to air qualitybull practicalities of making measurements

for research type approval testing andin-service policing

bull practicalities and cost effectiveness of achieving the standards through (for example) fuel specification engineoptimisation after treatment or traffic management

bull evaluation of potential side-effects ofproposed emission countermeasures4

it would be imprudent toignore a probable causal linkbetween particulate exposure

and acute health effects

Much research has to be undertaken and the results co-ordinated in order togenerate the necessary data to address theabove factors

The EU Commission has agreedsuggestions for particulate emissions fromdiesel passenger cars (on the modified cycleeliminating the first 40 seconds of idle) of 005 gkm for the year 2000 (Euro 3) and indicative proposals for 0025 gkm for 2005 (Euro 4) No standards were set for gasoline fuelled vehicles5 At this stage no recommendations were made on the introduction of particle sizedistribution criteria

Current vehicle emissions legislation isbased on the total mass of particles emittedper km with environmental legislation basedon a mass per unit volume basis with noreference to the size of the particles or thenumber concentration of particles emittedHowever regulatory bodies are consideringthe need to account for particle size in futurevehicle emission regulations As a precursorto this process studies have beenundertaken to assess the capabilities of available particle-size distributionmeasurement techniques in order toestablish the validity of past and currentassessments of the effects of (for example)fuel vehicle and drive cycle on particle sizedistribution (and perhaps composition)

Such studies are a necessary precursor tothe establishment of legislation and to thespecification of facilities required for typeapproval testing A further requirement maybe the development of appropriate lesssophisticated equipment for in-servicetesting Whilst initial steps have been madetowards the later objective particulate sizingmeasurement technology tailored to theneeds of vehicle emissions regulations isarguably at an early stage of evolution VAM

has been addressing the issue of standardprocedures for the generation andmeasurement of ultrafine particles over therange identified with vehicular emissions andwithin the context of the lsquoparticulates andaerosolsrsquo programme The primary aims ofthese on-going studies are tobull develop techniques for the

generation of well-defined ultrafineairborne particulates

bull improve the quality of suchmeasurements

bull develop tools and lsquoknow-howrsquo to implement best practices

bull work towards comparability of measurementsFurthermore uncertainties and current

difficulties with these measurements andtheir direct role with respect to legislationand product development have beenfundamental driving forces for the setting upof the Vehicle Particle Emission Club It hasbeen decided through consultation withindustry government and academia thatthere is a need for a Vehicle Particle EmissionClub (VPEC) The formation of the club issupported by the UK Department of Environ-ment Transport and the Regions (DETR)and DTINMSPU (VAM programme)

Why particles

Over the past few years UK needs withrespect to particle measurements have beenevaluated for the UK government6 byundertaking two market surveys78 and bythe contractor (AEA Technology plc)maintaining regular contact with UKindustry through the National Forum ForParticle Measurements (NFPM) Thisforum has assisted greatly in theidentification of particle measurement issuesthat can be addressed to the benefit of UKindustry (eg specification of calibrants andrequirements for sampling guidelines andmeasurement procedures) Typically theforum meets annually and consists of up to30 members from UK industry (chemicaland drug manufacture instrumentmanufacture and supply) regulatory bodiesconsultancy services and academia

Why vehicle particles

Transport is a major source of particlepollution and there is a body of evidence tosuggest that future emissions legislationwithin Europe and the US will include a


PMx ndash Particle Mass lt xmicrog


reduction in particulate emission levelscoupled with a degree of size discriminationNumber concentration limits may also beadopted in Europe depending on theoutcome of new research programmes

Vehicle particulate emissions have thepotential to cause adverse health effectsThese effects include cancer and otherpulmonary and cardiovascular diseases

Why a vehicle particleemission club

Particle emissions is a strategic area underclose scrutiny from the Government industryand the scientific community Industrycontinues to invest in new technologies (forexample lower emission engines abatementtechniques and low-sulfur fuels) in order toreduce these emissions Underpinning theseproduct developments and their broadacceptance are high-quality emission and airquality measurements

the measurements made on vehicle emissions will becritical for the development

of new legislation

Over the next few years the measure-ments made on vehicle emissions will be

critical for the development of newlegislation (if required) that is both wellreasoned and fair to all parties concerned

Thus careful consideration needs to begiven to the reasons for performing anyaerosol particle-size measurement If theresulting data is not suitable for the intendedapplication the measurements are worthlessBy way of an example if the user isinterested in the lung deposition of aparticular aerosol ensemble it is pointlessexamining the aerosol particles beneath amicroscope and determining a sizedistribution based on an equivalentgeometric diameter The measurement maybe accurate and precise but will not be fitfor purpose or relevant as the deposition ofthe particles within the lung will dependupon their aerodynamic diameter and nottheir equivalent geometric diameter Greatcare must be taken in the choice ofmeasurement technique Measurementobjectives for the club include helping themembers in the followingbull make the most appropriate choice

of instrumentationbull ensure that data produced is valid

in terms of accuracy and precisionbull ensure that all particle measurements

have an associated uncertaintybull ensure that traceable calibration

procedurestechniques are available

Key technical issues

Various elements of the VAM

programme have highlighted the following

key issues to be addressed in research aimed

at specifying particle size measurement

procedures relevant to vehicle emissionsbull sampling conditionsbull merits of number- andor

mass-based measurementsbull validation of instruments by

monitoring vehicle emissionsbull inter-instrument correlationbull development of standard sampling

and measurement procedures

Development of workplan

VPEC has four key objectives namelybull improve the quality and value of

the measurementsbull develop tools and lsquoknow-howrsquo

to implement best practicebull work towards national and international

comparability of measurementsbull provide knowledge on international

developments in health effectsmeasurement and test methodsstandards collection of data and testmethods and facilitate networking

Four work areas have been identifiedbull measurement and uncertaintybull environment and health impact

of emissionsbull combustion and particle formationbull context and gearing

Measurement and uncertaintyThere is no fixed methodology for making

particle size measurements of vehicle

emissions Factors that are likely to be

important include selection of most-

appropriate equipment dilution (ratio rate

mixing time etc) environmental conditions

(temperature humidity) and sampling

Environment and health impactParticles arising from engines are only one of

many sources of ambient particulate matter

Therefore it is difficult to measure the

exposures from various sources and to

distinguish the potential health risks

attributable to exposure to vehicle emissions

from those attributable to other air

pollutants As is frequently the case in

epidemiological studies of air pollutants

exposure to vehicle emissions was not



addressed nor the actual emissions from the

source of exposure characterised for the

period of time most relevant to the

development of health effects The under-

standing of the relationship between tail

pipe urban and personal exposure of

vehicle-produced pollution is clearly an

important goal for industry and government

Combustion and particle formation

ldquoUnderstanding the fundamental science

underlying particle formation and measurement

is critical to research organisations such as

universities health and environmental

organisations and local state and federal

governments Future low-emission engines must

be designed with an understanding of particle

formation and measurement Sound science

dictates that future environmental decisions

be based on understanding of the causes and

effects of pollutionrdquoldquoReview of Diesel Particulate Matter Sampling MethodsrdquoKittelson Arnold Winthrop and WattsUniversity of Minnesota January 1999

Context and gearing Following thecumulative worldwide interest and concernrelating to the potential health effects ofinhaled particles and recent reports on airquality trends new literature on health effectsmeasurements and test methods collection ofdata and test methods from national institutesresearch institutes universities industrialgroups and other relevant bodies is beinggenerated at an increasing rate Consequentlyit is important that the clubbull keeps abreast of this literaturebull communicates with the research

institutes universities industry groupsand other relevant bodiesAn agreed work plan has been developed

to address these requirements ensuring thatthe lsquoproductsrsquo and lsquoknow-howrsquo arising out ofthe clubrsquos activities are integrated respectedand valued within the community

Workplan prioritisation

Using the results from a market survey ofinterested parties a prioritisation of the clubrsquosinitial work programme has been carried outThe survey asked the recipients to rank (scaleof 1 to 5 where 1 is very low and 5 is very high)the priority for approximately 40 research topicsunder the 4 work areas discussed above


bull Networking with all Market Sectors (Government Industry Academia)

bull Cost-effective Development of ldquoProductsrdquo amp ldquoKnow-Howrdquo

bull Improvements to the Quality and Value of the Measurements Made

bull Tools that Underpin Product Development

bull hellipetc

OUTPUTS

BENEFITS

Figure 2 Summary of the results for the 4 work areas

Figure 1 VPEC Objectives

Measurement

bull Improve the quality and value of the measurements made

bull Develop tools and ldquoknow-howrdquo to implement best practice

bull Work towards national and international comparability of measurements

Information Management

bull Provide knowledge on international developments in health-effectsmeasurement and test methods standards collection of data and test methods

bull Facilitate networking

Measurement

bull Measurementintercomparisons

bull Best Practice SamplingMethods

bull Best Practice MeasurementMethods

bull Calibration Principles

bull New Tools for Measurement

bull QAhellipetc


bull World Wide Web-site (www)

bull Position Papers(1)

bull hellipetc

Industryrsquos concerns resulted in themeasurement and uncertainty work areabeing ranked highest and thus both the VAMprinciples and VAM funded activities in thisfield are both highly relevant and valued

These results for the four work areas willbe used to define a work programme that willbe carried out by the members (co-ordinatedby AEA Technology) Since the membershipwill include government industryprofessional bodies and academia theoutputs from the club are expected to assistin the formulation of both legislation andproduct development an example of VAMworking to the clear benefit of all sectors

For further information concerning airquality and vehicular emissions please contact

Dr David Booker AEA Technology Environment E6 Culham Abingdon Oxfordshire OX14 3ED UKTel 01235 463159 Fax 01235 463050 Email DavidBookeraeatcouk

REFERENCES

1 COMEAP Department of Health

Committee on the Medical Effects of Air

Pollutants Non-biological Particles and

Health HMSO London 1995



Pollutants Asthma and Outdoor Air

Pollution HMSO London 1995

3 EPAQS Department of the Environment

Expert Panel on Air Quality Standards

HMSO London 1995

4 Bagley S T et al lsquoCharacterisation of

Fuel and Aftertreatment Device Effects

on Diesel Emissionsrsquo HEI Research

Report No 76 Sept 1996

5 Dunne J M lsquoStates of Emissions

Legislationrsquo Proceedings of seminar on

lsquoApplication of Powertrain and Fuel

Technologies to meet Emission

Standardsrsquo IMech Eng London June

1996

6 Department of Trade and Industry

National Measurement System Policy

Unit VAM programme

7 Survey of User Needs AEA Technology

Report AEA-EE-0442 1993

8 Evaluation of Industrial Needs in Particle

Measurements AEA Technology Report

AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction

Physical methods of quantitative chemicalmeasurement are typically based on

spectra from one or more types ofspectrometer Spectra give you peakscorresponding to particular components ofthe sample with the size of the peak beingrelated to the quantity present Two types ofuncertainty are important Firstly theresolution of the spectrum should be as highas possible to distinguish between different

possible analytes Secondly the noise in thespectrum should be as low as possible togive the best possible estimate of thequantity of the analyte The constraints ofphysics engineering and economics meanthat the balance of these two uncertainties isoften not ideal Often an analyst may wantmore resolution at the expense of increasednoise or less noise in exchange for slightlypoorer resolution These days the balancecan be shifted by processing in software afterthe spectra have been recordedDeconvolution gives more resolution at theexpense of increased noise while smoothingreduces noise in exchange for slightly poorerresolution Deconvolution has its ownsubtleties but smoothing is a more stableoperation which can improve the precisionand reduce analysis time Smoothing isparticularly useful in those spectroscopies

where the signal is low perhaps withindividual photons or electrons beingcounted X-ray photoelectron spectroscopy(XPS) and Auger Electron Spectroscopy(AES) are particular examples sensitive tothe outermost atomic layers of a sample theygive spectra with typically between 1000 to100000 counts per channel of the spectrumwith most XPS spectra containing regions ofa few thousand counts or less We willreview the smoothing methods available andthe trade-offs they entail i l lustratingparticular points using examples from XPSand AES

There is an extensive literature onapplications of smoothing techniques toscientific data in general and to chemicalmeasurements in particular Introductorybooks on the subject include lsquoData Fitting inthe Chemical Sciencesrsquo by Gans1 and from a

Spectra in quantitative chemical analysis I Smoothing to reduce noise

more statistical point of view lsquoAppliedSmoothing Techniquesrsquo by Bowman andAzzalini2 We shall describe what is gained andwhat is lost by smoothing This leads torecommendations on when to smooth and howbest to apply smoothing in practical situations

Why smooth

Smoothing in the general scientificliterature has acquired a rather shakyreputation Strangely enough if the sameproblem is recast in the Fourier domain and aWiener filter applied this is often viewed asmuch more rigorous even though the twoprocesses can be mathematically identical Itcan be something of a culture shock forscientists or engineers new to spectroscopy tofind smoothing is so extensively usedExperienced XPS and AES users know howvaluable it can be and many spectra aresmoothed especially for presentation purposes

When to smooth Smoothing is best used as a method of

guiding the eye by using your knowledge ofinstrument resolution and the noisedistribution of electron counting toeliminate as much as we can of the noise in aspectrum revealing features which the eyecan then identify as being significant Thismay be particularly valuable when dealingwith large numbers of spectra for exampleas part of a montage to be presented to acustomer An intelligent choice of smooth toapply to a set of data of this type may bringout features clearly which would otherwisebe lost in the noise especially for aninexperienced customer In contrast anexperienced analyst has likely alreadyacquired the skill of rejecting the noisy partof the spectrum when lsquoeyeballingrsquo dataSmoothing can help the less experienceduser or customer spot some feature whichthe experienced analyst might spot straightaway in the raw data

One application which proves to be veryuseful in practice is the mitigation of errorsin software which can make algorithms forspectral processing much more sensitive tonoise than they should be Though not anideal solution the performance of faultysoftware can be improved substantially bypreceeding it with an appropriate smooth

Quite often in quantitative analysis onewishes to compare properties of a set ofpeaks which have a simple geometric

interpretation Peak height ratios and fullwidth half maxima are typical examples butthere are many cases where one wishes tocompare other measures such as the heightof the peak ratioed to the height of thebackground in some other region of thespectrum Experience shows that suchsimple geometrical ratios combined withsome physical and chemical insight can leadto very precise measures of systematicvariations in chemistry across a range ofsamples Smoothing can help here becausewhat is needed is a geometrically simple wayof averaging over a small number ofchannels If one had the time to set up such acalculation one might do this by least-squares fitting to polynomials In practice thetime involved in setting up such a fit woulddetract from the simplicity and speed of thegeometrical approach while smoothing (forexample by one of the Savitzky-Golaymethods) gives a result which is virtuallyidentical mathematically but can beperformed in seconds using softwareavailable on virtually every data system

Therefore the most justified use ofsmoothing is forbull presenting noisy spectra for

qualitative analysisbull mitigating the effects of quantification

software which is more sensitive to noisy channels in the spectrum than it should be

bull improving the precision of simplegeometrical ratios taken from spectrawhich can often be very precisemeasures of changes in chemistry

When not to smooth

Smoothing needs most care when

performed before any kind of quantitative

analysis such as in least-squares fitting

measurement of Full Width Half Maxima

(FWHM) or peak-to-peak heights Even so

the correct choice of smooth can often result

in a negligible error in these subsequent

quantitative analysis steps For example the

Savitzky-Golay smoothing methods1 can be

chosen so as to have a negligible effect on

both peak height and peak width while

suppressing noise very effectively However

the proper choice of the width this smooth is

critical and the choice of the width for this

smooth is an important topicSmoothing should never be done if one

is subsequently to use any statistical method

which assumes the counts in each channel tobe independent measurements Aftersmoothing they are no longer independentbut instead are partly correlated Anexample of this is in the use of x2

to judgegoodness-of-fit to a model spectrum Manycommercial software systems report thelsquoReduced Chi-Squaredrsquo value to the userafter fitting and one quickly learns torecognise that fits which appear good to theuser have a reduced x2

of about unitySmoothing before fitting will systematicallyreduce the value of x2

so that it can nolonger be used as evidence of the fit being agood one At worst it could mislead one intoaccepting a fit which is visually poor onspurious statistical groundsbull Avoid if possible smoothing before

quantitative analysis for example fittingthe spectrum to a model or beforemeasurement of parameters like peakheight or width

bull If smoothing is unavoidable choose thenumber of points in the smooth verycarefully to avoid adding a systematicerror to the quantity you are trying tomeasure

bull Treat with special caution statisticalmeasures such as x2

values which canbe altered by smoothing

Savitzky-Golay smoothing

This smoothing method is math-

ematically equivalent to fitting a polynomial

of degree m to P=2m+1 channels and taking

the value of the polynomial as the value of

the centre channel Popularised by Savitzky

and Golay4 (see also later corrections5 to

their coefficients) the method was used

earlier6 possibly even back to the 19th

century1 Seah and Dench7 examined

applications of Savitzky-Golay smoothing in

AES and XPS Bromba and Ziegler8 showed

Savitzky-Golay smoothing to give essentially

the best reduction of noise in the limit of low

peak distortion Two variants of Savitzky-

Golay smoothing need to be discussed in

detail These are the Savitzky-Golay

quadraticcubic smoothing function and the

Savitzky-Golay quarticquintic smoothing

function It is worth taking a moment to

understand why these smoothing functions

have the names that they do since this is

seldom explained in the documentation

accompanying software which performs




smoothing A detailed mathematical analysis

of piecewise polynomial fitting shows that

provided one is dealing with an odd number

of points fitting a quadratic (parabola)

function leads to exactly the same equations

as a cubic function and similarly fitting a

quartic function leads to exactly the same

equations as fitting a quintic8 Thus the

Savitzky-Golay quadraticcubic smooth for

example could be derived from either

piecewise fitting of quadratic functions to the

data or piecewise fitting of cubic functions to

the dataZiegler9 listed a number of important

properties of Savitzky-Golay smooths ofwhatever order the first five of those helisted are the most importantbull They preserve any symmetry (evenodd)

contained in the signal bull The position of symmetric (spectral)

lines of any shape is preserved exactly bull The area under any signal curve is

preserved exactly bull The centre of gravity of any signal curve

is preserved exactly bull For filters with quadratic order and

above the second moment of (spectral)lines is preserved exactly Since thissecond moment is the true measure of the line width this is especiallyimportant in spectrometry In otherwords for Savitzky-Golay filters haveonly a second-order effect on increasingthe peak FWHM not a first order effect as do other filters such as inGaussian smoothing

The properties of Savitzky-Golay smooth-

ing are neatly summarised by Press et al10

Within limits Savitzky-Golay filtering doesmanage to provide smoothing without loss ofresolution It does this by assuming thatrelatively distant data points have somesignificant redundancy that can be used toreduce the level of noise The specific nature ofthe assumed redundancy is that the underlyingfunction should be locally well-fitted by apolynomial When this is true as it is for smoothline profiles not too much narrower than thefilter width then the performance of Savitzky-Golay filters can be spectacular When it is nottrue then these filters have no compellingadvantage over other classes of smoothing filter coefficients

Later in this article Figure 5 will allowus to fix a firm numerical value for lsquonot toomuch narrowerrsquo

Properties of Savitzky-Golaysmoothing functions

Savitzky-Golay smoothing offers twomain families of related smoothing functionswhich differ only in the number of channelsover which the smooth takes placeHowever if one plots each family in reducedform as shown in Figure 1 one can see thatas the number of points in the smoothincreases the quadraticcubic smoothingfunctions rapidly become very similar TheSavitzky-Golay quarticquintic smoothshows this property too as shown in Figure2 as the number of points increases a limitingfunctional shape is quickly approached

One can easily see from Figures 1 and 2that convergence to a consistent smoothingfunction is relatively rapid as one increasesthe number of points in the smooth Theconclusion we should draw is that theperformance of the smoothing functionsdepends not so much on the number of

channels chosen but on the total width of

the smoothing function especially in relation

to the size of features in the spectrum to be

smoothed It is therefore useful to compare

the noise reduction performance of the

quadraticcubic and quarticquintic Savitzky-

Golay smooths when applied to spectra with

the range feature size specifically peaks with

a range of full width half maximum What

the previous two figures tell us is that the

number of points in the smooths does not

strongly affect performance so we will plot

the results assuming a very large number of

points in the smooth

To compare the effects of different kinds

of smooth let us look at the separate effects

of the smooth on the spectrum and on the

noise Measured spectra of course are an

inextricable mixture of the two Therefore we

shall compare the effects of different smooths

on model spectra and model noise plotted

separately The model spectrum we shall use

shown in Figure 3 consists of nine peaks of

progressively larger full-width at half

maximum each having a peak height of 1000

counts per channel on a background of 4000

counts per channel Before smoothing the

noiseless spectrum and the separately plotted

noise are as shown in Figure 3

Note however that the number of points

one chooses in practice is very important

largely because it defines the width of a

smoothing function in relation to the feature

size of the spectrum you want smooth So

when you come to apply a Savitzky-Golay

smoothing in practice a sensible choice for

the number of points in the smooth is

essential Figure 4 is a tableau showing the


Figure 1 Satvitzky-Golayquadraticcubic smoothingfunctions Smooths are of P=5 points (dotted) 7 points(dashed) 15 points (dash-dot) and 1001 points(continuous line)

To emphasise how closely related thesesoothing functions are we have plotted them on axes scaled by m=(Pndash1)2 otherwise thenormalisation of their areas tends to obscuretheir similarity k=ndashm ndashm+1 hellip mndash1 m is thechannel number with respect to the channelbeing smoothed so that the centre channelcorresponds to k=0 Clearly an asymptotic shape for this filter function is reached rapidly

Figure 2 As for Figure 1 but plotted for the Savitzky-Golay quarticquinticsmoothing function Here P=7 points (dashed) 15 points (dash-dot)and 1001 points (continuous line)

As was the case with the quadraticcubicfunction an asymptotic shape for thequarticquintic function is reached rapidly


effect of Savitzky-Golay smoothing with four

different choices for the number of points in

the smooth We can immediately make a number of

useful observations from this tableau For anygiven number of points in the smooth themoving average method leads to moredistortion than does the Savitzky-Golayquadraticcubic which in turn leads to more

distortion than the Savitzky-Golayquarticquintic Whatever kind of smoothingis applied sharper peaks suffer the greatestdistortion When the number of points in thesmooth is large and the peak is sharp aftersmoothing the peak tends to look more likethe smoothing function than a spectroscopicpeak at all In particular for the two Savitzky-Golay smooths shown the narrowest peakscan exhibit negative going wings WhicheverSavitzky-Golay smooth is chosen similarlevels of noise reduction lead to similar levelsof peak distortion One can see this bycomparing the 15-point quadraticcubicsmooth and the 23-point quarticquintic one

The noise level after each of these twosmooths and the distortion introduced byeach smooth is virtually identical The 7-point moving average smooth causes similardistortion to the 15-point quadraticcubicsmooth and the 23-point quarticquinticone but leaves marginally more noise

Choosing the right Savitzky-Golay smooth

We can compare the lsquotrade-offrsquo betweenremaining noise in the spectrum and peakdistortion both of which we wish tominimise Figure 5 shows this trade-offcurve for four different types of smoothing

including both Savitzky-Golay quadraticcubic and quarticquintic for both Gaussianand Lorentzian peak shapes The majority ofpeak shapes in electron spectroscopy fallsomewhere between these two extremesOne can see in Figure 5 that

bull for a smoothing width to FWHM ratioof up to about 02 Savitzky-Golayquadratic cubic smoothing leads tovirtually no distortion to either peak-height or peak width

bull for a smoothing width to FWHM ratioof up to about 03 Savitzky-Golayquarticquintic smoothing leads tovirtually no distortion to either peak-height or peak width

bull beyond this the amount of distortionyou are able to accept depends on yourapplication Sherwood suggests anupper-limit of 10 for this ratio forquadraticcubic smoothing and 17 forquarticquintic smoothing Both causeapproximately 15 loss of peak heightand less than 25 broadening of aGaussian peak3


Figure 3 Specimen datacomparing the effects ofsmoothing proceduresThough it is impossible to do for real data here weplot the true spectrum and the noise on that spectrumseparately This spectrum consists of nine peaks ofincreasing FWHM so that the effects of smoothingcan be compared Here we have chosen an exampleof peaks with 1000 counts at their maximasuperimposed on a constant background of4000 counts The noise shown on the lower plotis for the Poissonian statistics of electron detection

Figure 5 Trade-off curves for Gaussian peak-shapesshowing the distortion ofpeak height and FWHM for a range of noise reductionsThe Savitsky-Golay functions give the best result for noise reduction and minimal distortionN is the number of channels within the FWHM of the peak (eg for a peak of FWHM 125eVacquired at channel separation 005eV N=25)Note that there is a clear point at which anyattempt to gain better noise reduction leads to significant distortion

Figure 4 Tableau showing the effect of employing differentnumbers of points in the smooth for three types of smoothing


Conclusions about Savitzky-Golay smoothing

Savitzky-Golay smoothing is the bestgeneral smoothing method available within awide range of surface analysis and otherspectroscopic software It improves signal tonoise without distorting peaks at all providedbull a sensible choice is made on them number

of points to smoothbull peaks are well approximated by

a polynomial

Gaussian smoothing

Gaussian smoothing can be seen as an

intermediary between simple moving average

smoothing (ie by a lsquotop-hat functionrsquo) and

Savitzky-Golay smoothing Intuitively one

feels that any successful smoothing method

should weight central points strongly and

peripheral points weakly This leads one to

any of a large number of bell-shaped

functions of which a Gaussian is simply the

most well known There is no fundamental

reason why Gaussian should give the best

possible performance in this role Instead

the justification for using it comes from its

simplicity and the fact that it will mimic the

effect of a large number of instrumental

broadening processes11 The Central Limit

Theorem12 from statistics tells us that

whatever the shape of these individual

instrumental broadening functions a large

number of them taken together will give the

instrument as a whole a Gaussian resolution

function Therefore Gaussian smoothing has

an almost pedagogic purpose in that the

effect is to mimic an instrument with poorer

energy resolution If one is aiming for the

best possible noise reduction with least peak

distortion then Savitzky-Golay smoothing

will always be superior if the correct width of

smooth is chosenThus Gaussian smoothing we can

conclude

bull improves signal to noise but always at

the expense of some peak broadening

bull is easy to visualise because Gaussian

smoothing is similar to decreasing the

energy resolution of an instrument

bull can make some kinds of quantitative

analysis more precise by degrading data

from different instruments to remove

the systematic effect of their different

energy resolutions

Other smoothing and filtering methods

Exponential filtering

This is largely of historical interest

being the simplest smoothing method to

implement electronically by means of a

simple lsquolow-passrsquo RC filter There are still a

few cases where this filtering is of interest to

the AES spectroscopist ndash for example when

acquiring direct spectra using beam-blanking

and lock-in amplifier followed by an

adjustable electronic RC filter As a method

of smoothing previously acquired spectra

however it has been shown9 to be inferior

to the Savitzky-Golay smoothing methods in

all conceivable spectroscopic applications

and is best avoided when developing

software for smoothing

Smoothing by taking the moving average This is sometimes known as a lsquotop-hatrsquo

smooth because the convolutionalsmoothing function is square and resemblesa top hat in cross-section This is very simpleto program but causes more distortion tothe peak than Savitzky-Golay smoothing forany given noise-reduction factor as can beseen in Figure 5 Savitzky-Golay smoothingwith the right choice of number of points inthe smooth can often achieve the samelevels of noise reduction with little or nopeak distortion

If one has a spectrum with a narrow

channel separation (perhaps 005eV or 01eV)

and facilities for other types of smoothing are

not available then a three-point moving-

average smooth will reduce the noise by a

useful 42 without causing unacceptable

distortion to spectra acquired in the range of

resolution 025 to 1eV which are typically used

Wiener filtering Sometimes known as lsquooptimalrsquo filtering

this is performed in Fourier space though it

can equally well be viewed in real space as

another type of convolutional smooth XPS

applications of frequency domain smoothing

(and deconvolution) have been discussed

by Wertheim13

When using any method with the word

lsquooptimalrsquo in its title one must take care to

understand what is being optimised Wiener

filtering is mathematically equivalent to a

smooth which attempts to minimise the

difference between smoothed spectrum and

true spectrum in the least-squares sense10

This difference comprises two sources noise

and the distortion due to smoothing This is

fine for some purposes and if implemented

using Fast Fourier Transform (FFT)

algorithms10 Wiener filtering will be very

fast However usually one would rather

optimise other aspects of a smoothed

spectrum for example minimising the

broadening of peak shapes at the expense of

reducing the spectrum noise a little less

Savitzky-Golay smoothing achieves this very

effectively with the right choice of number of

points in the smooth Note that is clear in

Figure 5 that any smoothing greater than the

optimal choice for the Savitzky-Golay

functions leads to strong distortion for very

small gains in noise reduction

The effect of Wiener filtering in practice

is very similar to a Savitzky-Golay smooth

using more points than recommended

above The result is a spectrum in which

noise has been very effectively suppressed

though at the expense of some energy

resolution which could have been retained

with the right Savitzky-Golay smooth

Nevertheless if easily available Wiener

filtering can be a very useful and powerful

smoothing method

Conclusions

bull The most generally useful kind of

smoothing is the Savitzky-Golay type

Considerations of noise reduction vs

distortion of the peak lead us to suggest

maximum smoothing widths of 10 and

17 of the peak FWHM for Savitzky-

Golay quadraticcubic and

quarticquintic smoothing respectively

bull For surface analytical spectroscopies

and specifically X-ray photoelectron

spectroscopy many peaks have a width

of 1eV and since high resolution data

are recorded at 01eV intervals a useful

choice is a 9 point quadraticcubic

Savitzky-Golay smooth For spectra

acquired at 005eV intervals a useful

choice is a 17 point quarticquintic

Savitzky-Golay smooth

bull Gaussian smoothing has some useful

special applications especially where

one needs to reduce a set of data are

acquired on several instruments to a

common low energy resolution


bull Very occasionally simple moving averagesmoothing may be useful when neitherof the two above methods are available

bull Wiener filtering is fast and in terms ofits effect on the spectrum will alwayshave a virtually identical counterpartfrom the set of Savitzky-Golay filters

REFERENCES

1 Gans P Data Fitting in the Chemical

Sciences Chichester UK John Wiley

1992

2 Bowman A W and Azzalini A Applied

Smoothing Techniques for Data

Analysis vol 18 of Oxford Statistical

Science Series Oxford UK Oxford

University Press 1997

3 Seah M P Dench W A Gale B and

Groves T E J of Phys E Sci Instrum

21 351ndash363 1988

4 Savitzsky A and Golay M J E Anal

Chem 36 1627 1964

5 Steinier J Termonia Y and Deltour J

Anal Chem 44 1906 1972

6 Guest P G Numerical Methods of Curve

Fitting Cambridge UK Cambridge


7 Seah M P and Dench W A Journal of

Electron Spectroscopy 48 43ndash54 1989

8 Bromba M U A and Ziegler H Anal

Chem 53 1583ndash1586 1981

9 Ziegler H App Spectrosc 35 88ndash92

1981

10 Press W H Flannery B P Teukolsky S A

and Vetterling W A Numerical Recipes

Cambridge Cambridge University

Press 1986

11 Evans S and Hiorns A G Surf Interface

Anal 8 71ndash74 1986

12 Bulmer M G Principles of Statistics

New York Dover 1979

13 Wertheim G K J Elec Spectrosc 6

239ndash251 1975

14 Proctor A and Sherwood P M A Anal

Chem 52 2315ndash2321 1980



C A S E S T U D Y

Dr SteveAshdownHuntsmanTioxideJohn Francisand KeithMarshallLGC

This is the fourth of a series of case studies of the business

benefits of VAM Companies oftenperceive the merit in sharing their ownstories of the tangible financial andtechnical benefits of the VAM approachIt is hoped that these articles will provideenough detail to be of value beyond theindustrial sector directly involved to awider range of businesses engaged inanalytical science

Summary

Huntsman Tioxide is a major inter-

national producer of titanium dioxide

pigments for the paints and plastics industry

The company operating in a specialised area

of the bulk chemicals industry has

independently arrived at the principles of

valid analytical measurement entirely from

business-driven considerations Foremost

among these were the need for global

uniformity of product and the need for

continuity of product specification at each of

the eight manufacturing sites worldwideThe companyrsquos story is taken up here in

1995 when despite substantial analyticalresources and a suite of documentedmethods the benefits of an analyticalperformance assessment programmebetween manufacturing sites had not yetbeen seized The subsequent success of aweekly check sample scheme led to thedevelopment of a more rigorous proficiencytesting scheme a system of internalreference materials and eventually to anethos of best practice sharing between thefar-flung analytical laboratories

Huntsman Tioxide now prepares to enterthe new millennium with validated methodsreflecting the latest analytical technology It isa company taking every opportunity tobenefit from international dialogue within its

Titanium dioxide manufacture a microcosm of analytical best practice


analytical community while making full useof the special process and analytical expertiseof its UK science base

Introduction

Huntsman Tioxide is strongly focusedon the production of titanium dioxide - asthe worldrsquos third largest producer of thesubstance it employs over 3000 people Thecompany has eight production sites globallyincluding five sites in Europe Titaniumdioxide is the most commonly used whitepigment with more than 3 million tonnesbeing used annually worldwide

Titanium dioxide production generallystarts from raw mineral sources (ilmeniteand mineral rutile) Chemical extraction bythe sulfate process (introduced in 1918) orthe chloride process (1958) is followed bymilling to a microcrystalline state Thestages of the processes are illustrated inFigure 1 Titanium dioxide product can bespecially processed and finished (forinstance with different chemical coatings) tosuit many applications A major market isthe paints and coatings industry for whichthe pigment treatment will depend onwhether the final coating product is intendedfor interior exterior or specialist use Otherindustrial processes using titanium dioxidepigment include the manufacture of plasticspaper inks ceramics rubber fibrestoothpaste and even foods such as mint-flavoured sweets (the pigment is otherwiseknown as additive E171)

In recent years the company has alsobuilt up markets for the co-products oftitanium dioxide production ndash carbondioxide iron salts and gypsum formed byneutralisation of spent sulfuric acid ndash withthe added benefit of reducing the environ-mental impact of waste from the coreproduction process Carbon dioxide can besold after liquefaction iron salts are used forwater treatment and soil improvement andgypsum is incorporated in plasterboard andcement The combined quantity of these co-products sold by Huntsman Tioxide 900 000 tonnes per annum is now greaterthan that of titanium dioxide itself

Role of analytical science in the business

It may be surprising to an outsider torealise that titanium dioxide pigment is a

C A S E S T U D Y

Figure 1 An outline of titanium dioxide production and processing


complex product characterised by manyanalytical parameters The UK site inBillingham Cleveland has well-equippedanalytical facilities and acts as a referencelaboratory for the companyrsquos other sitesElemental assay has an important role in thebusiness with the analytical suite includingX-ray fluorescence (XRF) and inductivelycoupled plasma mass spectrometry (ICP-MS) All sites maintain quality control andapplications testing laboratories whichgenerally bear the brunt of the involvementin process management and recognise theleadership role of the larger and morediverse UK laboratory on broader issuessuch as analytical harmonisation

titanium dioxide pigment is a complex product

characterised by manyanalytical parameters

A titanium dioxide pigment specificationtypically includes the parameters shown inTable 1 VAM principle 1 (Analytical measure-ments should be made to satisfy an agreedrequirement) is fulfilled by product develop-ment activities which provide a sufficientlydetailed product specification to meet the

corporate perception of customerrequirements Analytical process monitoringand quality control functions determinewhether the specified parameters are met towithin predetermined tolerances There maybe several tolerance levels corresponding tothe grade (and thence the value) of product

Drivers for proactive quality management

The VAM programme strongly supportsconsistent analytical measurements bothbetween laboratories and with the passage oftime These same aspects of measurementconsistency were important to Huntsman

Tioxide in achieving its production qualitygoals of providing consistent productsglobally across its production sites inEurope North America South Africa and theFar East All means advocated by the VAMprogramme for achieving these goals have aplace in the companyrsquos growing commitmentto consistent analytical measurement

The situation in 1995

The company had an established corpusof methods documentation The methodswere classified into books treating the broaddivisions of analytical science relevant to thecompany primarily as lsquophysicalrsquo orlsquochemical and environmentalrsquo secondarilyby technique or application Full methodsdocumentation was distributed to each sitefor use in quality control and applicationstesting functions thus supporting VAMprinciple 6 (Organisations making analyticalmeasurements should have well defined qualitycontrol and quality assurance procedures)

However in 1995 the company had littlein the way of interactive checking andcomparison between its sites to ensure thatthe methods were followed and were fit for

delivery of the required product uniformity(uniformity being assessed for each analyteagainst a tolerance about a specifiedconcentration or other measured value)

Improving productconsistency

Huntsman Tioxide has continuouslyimproved its approach to analyticalcomparability between its sites since 1995and this effort has been rewarded with anincreasingly consistent product The firststep in this process however wasrecognition of the need to improve asillustrated by the following scenario

C A S E S T U D Y

Rotary calciners used in the production of titanium dioxide

Physical properties Dry and wet particle size

Crystal form (percentage of rutile or anatase form)

Chemical properties Elemental assay (especially Al Si Zr Fe P K)

Determination of natural impurities monitoring of internal additives and particle coatings

Applications properties Colour

Durability (weather resistance)

Light fastness (stability of colour)

Opacity

Gloss

Table 1 Analytical parameters for the development and qualitycontrol of a titanium dioxide pigment

A trial of a new standard productspecified according to Table 1 was carriedout at an overseas plant followed by scale-upat a second overseas site The materialsproduced at these plants were analysedrepeatedly in the UK and were found to besignificantly different despite use of the samespecification The reason was that localanalytical data had been fed back into theadjustment of process parameters and thatalthough the same methods were supposedlyin use throughout the company localvariations in analytical measurement hadresulted in divergent adjustments being made

In 1996 critical parameters for

development of this product were identified

and a system of weekly testing was

inaugurated Six samples were taken from

the production plant for each participating

site ndash three of these were taken from a

definite point in the middle of the process

and the remaining three were taken at the

end of the process The samples were

analysed in the UK for repeatability which

is essential to achieve tolerances of the order

of plusmn001 for critical elements The level of

agreement between sites was also monitored

Early in 1998 the weekly testing system

was rolled out across the company Although

led centrally by the UK this initiative was

canvassed and accepted internationally as

being critical to achieving consistent and

identical products from different factories

and so providing security and status for the

local factory in relation to the company as a

whole The roll out was motivated by the

need to comply with a tighter product

specification Another factor was the need to

offer reliable confirmatory analysis at all

Huntsman Tioxide sites on product

transported internationally from the site

of manufacture

Proficiency testing

A centrally co-ordinated sampledistribution scheme was subsequentlyadopted to ensure that the local laboratoriescould be assessed independentlyParticipating sites received samples onceevery three months Six to twelve samples ofunstated composition were distributed toeach participant Each set included replicatesamples not marked as such to allow theassessment of repeatability The companywas in fact evolving an internal proficiency

testing scheme akin to the schemes inspiredby VAM principle 4 (There should be a regularindependent assessment of the technicalperformance of a laboratory)

Progress was monitored centrally for bothweekly check samples and quarterly proficiencytesting (PT) results Central monitoringallowed a comparison of the performance of allsites (and consequently indicated any localproblems) as well as an absolute assessment ofprogress towards corporate targets forcompliance with product specification Arating system was introduced to provide afurther incentive for compliance to the schemeThe system was weighted to rewardparticipation (the submission of completeresults sets) as well as performance (accurateand precise results) High scoring laboratorieswere offered the carrot of exemption from theweekly check scheme provided thatperformance was maintained in the quarterlyPT rounds Substantial year-on-yearimprovements have resulted in most cases

Reference materials

Only one independently certifiedtitanium dioxide reference material has beenavailable to Huntsman Tioxide Further-more the company is currently experiencingsupply problems with this material ndash and thematerial is certified only for titanium dioxidecontent whereas product quality alsodepends critically on the control of impuritiesand additives While recognising that itwould be advantageous to use independentreference materials for titanium dioxidepigments Huntsman Tioxide has thereforebeen compelled to use its own system ofinternal reference materials throughout thecompany contributing to a position inaccord with VAM principle 5 (Analyticalmeasurements made in one location should beconsistent with those elsewhere)

The internal reference materials havebeen produced in the UK and haveundergone homogeneity testing Sufficientstocks are maintained to prevent the supplyproblems frequently encountered withindependently produced reference materialsElemental concentrations have beenassigned by the consensus of results from theindependent (orthogonal) techniques ofatomic absorption atomic emissionspectroscopy mass spectrometry andclassical methodology The materials alsoundergo batch-to-batch comparison tests

The established corporate analytical

methods have been revised to specify clearly

the reference materials that are acceptable

for intercomparison purposes within the

company There are presently 35 such

materials but it is intended that the system

be simplified to comprise 12 fully

characterised materials

Analytical methods recent developments

The highest hurdle in method validation

is frequently the requirement to show that

the method can produce the same results in

different laboratories In a global business

for which the method must be translated into

several languages there is an increased risk of

difficulties arising at this stage The company

now provides translations of methods at

source to minimise local variation

Huntsman Tioxide has the benefit of

detailed written analytical methods but has

recently become more acutely aware of the

need to adapt to the rapid developments in

analytical instrumentation Also the less

glamorous but critical activities of sampling

and sample preparation sometimes receive

limited attention when methods are drafted

Originally the companyrsquos methods were

written with a single instrument in mind The

application of a completely new technique to

a particular analyte will generally attract wide

attention and will be accompanied by a new

written method for example microwave

methods in elemental assay have recently

been added to the corporate documentation

However it often happens that certain details

of established methods are irrelevant to users

of slightly different instrument models and

method variants can be substituted without

consultation The company is developing a

communications culture of proactive feedback

from local sites followed by discussion and

method revision managed centrally

A forward looking culture

Huntsman Tioxide has achieved a greatdeal of visible progress in analyticalperformance over the last five years asevidenced by long term PT scheme recordsProgress to date has required thedetermination and persistence that go with aforward-looking culture The company hasalso recognised the prerequisite of staff


C A S E S T U D Y


training and competence for obtaining validanalytical data (VAM principle 3 ndash Staffmaking analytical measurements should be bothqualified and competent to undertake the task)Training needs are identified locally and theemphasis of the overall training programmeis adjusted to address those needs Specialisttechnique training is available from thecentral UK facility so as to provideconsistency and is delivered both in the UKand on site

The company has now introducedinternational quality audit procedures in aphased programme which began late in 1998and a Harmonisation Forum was held in mid1999 The Forum spent three days reviewingthe corporate methods and disseminatingbest practice between its sites It was madeclear to all participants that change wasessential to the harmonisation processControl charts were to be used at all sites fora specified number of daily quality controlsamples Statistical techniques were used toset levels of analytical replication appropriateto each method based on the precision of themethod and the required level of compliancewith product specification

The first set of site audits was completedbetween Autumn 1998 and Spring 1999aiming not merely to assess performance butto provide consultancy and support where

needed across the company Drafts of thefully revised methods documentation arebeing evaluated until October 1999 (VAMprinciple 2 ndash Analytical measurements shouldbe made using methods and equipment whichhave been tested to ensure they are fit for theirpurpose) after which full implementation willbe required A further cycle of auditsscheduled for 2000 will focus onperformance assessments for the analysis ofcritical elements accompanied by a reviewof best practice widened in scope to includefurther compositional parameters

The business benefits of VAM

bull There has been a year-on-year

improvement in conformance of the

product to specification providing the

ability to deliver continuity of

specification to customers with a long

term requirement and increasing

customer confidence in the reliability

of the product

bull A programme of international

harmonisation has improved product

consistency globally allowing customers

to be reassured if sources of production

are switched and offering efficiency

improvements to customers with

multinational operations

bull The product is meeting progressively

tighter specification limits resulting in

an increased value because it is classified

as of a higher commercial grade

bull Complicated production processes may

require the feedback of analytical data to

adjust process parameters The feedback

will only be useful if the analytical data is

valid and fit for this purpose

bull VAM offers principles as standards and

goals for the analytical community but

is not prescriptive Analytical sectors and

groupings are able to develop VAM in a

realistic context Instances arising from

this study are the production of specialist

reference materials and the choice of

approach to value assignment for such

materials (by a reference laboratory in

this case)

bull Although operating in a specialised niche

of the chemicals sector and initially

isolated from the VAM initiative as

applied elsewhere business objectives

dictated the independent development

of an approach closely similar to VAM

at Huntsman Tioxide Such lsquoconvergent

evolutionrsquo towards valid analytical

measurement powerfully endorses the

role of the VAM principles throughout

analytical science

C A S E S T U D Y

V A M I N E D U C A T I O N

Two years ago all UK chemistry

departments received materials relating

to quality assurance in analytical chemistry

the lsquoTertiary Education Resource Packrsquo This

resource was designed for use by teachers and

lecturers at the tertiary level who either want

to develop a course module on quality in

analytical chemistry or who want to import

new ideas and materials into existing courses

Following feedback from recipients the

original paper based version has been

converted to a web-based format to facilitate

more effective distribution Hopefully this will

make it easier for those involved in teaching to

down load relevant materials New articles

and case studies have been added to the

resource and the bibliography and glossary of

terms sections have been updated

The material has been designed to be

modular lecturers can dip into the contents

and take out those sections that they

consider will be most useful It should be

viewed more as one source amongst several

others The lecturer might wish to abstract

sections to help put together the particular

course that shehe has to deliver Several

articles can be down loaded to facilitate

copying To fit in with its new image the

resource has a new title lsquoQuality assurance

of chemical measurementsrsquo This indicates

that it has wider applications than just

tertiary education

Although the topics covered in the

resource relate immediately to analytical

chemistry we would strongly recommend

lecturers in other branches of chemistry to

consider using some of the material Part of

the reason for this is that the successful

pursuit of all branches of chemistry relies to

a greater or lesser extent on chemical

measurement The synthesis of a new

compound or the identification of a new

Resource for Quality Assuranceof chemical measurements

mechanistic route is often critically

dependent upon confident knowledge of the

starting materials intermediates and final

products Provision of information on what

is present and in what amount is the job of

the analytical chemist It is only possible to

make proper use of the analytical data if the

worker who commissioned the analysis

appreciates the capabilities and limitations of

analytical science

The resource is available on the VAM

web site (wwwvamorguk) Select lsquoQA of

chemical measurementsrsquo from the screen

side menu Selecting the items from the

screen side menu will direct you to the

appropriate part of the resource whereas the

buttons on the top of the screen will direct

you to other parts of the web site Please do

browse around there may be more that

interests you There are no restrictions on

copying any of the material provided the

source is acknowledged

This resource has been produced atLGC in conjunction with professionalanalysts and academic staff as part of theVAM programme

For further information and commentsplease contact

Pete HoulgateLGCTel 020 8943 7457Fax 020 8943 2767Email prhlgccouk



R E F E R E N C E M A T E R I A L S U P D A T E

L GC continues to supply an expandingrange of reference materials to assist

analysts throughout the world Use ofreference materials increases confidence inanalytical results and is a useful tool forlaboratories seeking accreditation A newseries of materials is now available fromLGC Analysis of environmental and foodsamples is particularly important and thenew selection of materials reflects this

Please contact LGCrsquos Office of ReferenceMaterials (ORM) for further informationand prices

The Reference Materials AdvisoryService (REMAS) will be pleased to offerfree advice if you have problems locating thedesired material (See back cover)

ORM staff will be pleased to discussreference materials and meet existing andpotential customers at the followingconferences amp exhibitionsbull Analytica 2000

(Munich Germany 11ndash14 April 2000)bull Achema 2000

(Frankfurt Germany 22ndash27 May 2000) Reference materials are also now available

from a new office in Sweden LGC NordicAB based in Borarings the home of SP theSwedish National Testing Institute

For further details contactLGC Nordic ABBrinellgaten 4PO Box 1737SE-501 17 BoraringsSwedenTel 46 (0)33 16531525Fax 46 (0)33 165310Email infolgcspse

Catalogue number Matrix AnalytesProperties CRMRM

EnvironmentLGC6144 Gas works - contaminated soil Leachable metals PAHs anions sulfur RMLGC6137 Estuarine sediment Leachable metals CRMLGC6156 Harbour sediment Leachable metals RMLGC6017 Rainwater - roof run-off Metals CRMLGC6018 Rainwater - roof run-off Anions CRMLGC6019 Riverwater - River Thames Metals CRMLGC6020 Riverwater - River Thames Anions CRMLGC6177 Landfill leachate Metals RMLGC6178 Landfill leachate Ammonia (as N) anions COD TOC RMLGC6147 Waste oil PCBs RM

FoodLGC7172 Dairy cattle feed Proximates elements RMLGC7173 Poultry feed Proximates elements RMLGC7106 Processed cheese Proximates RMLGC7104 Sterilised cream Proximates elements RMLGC7150 Processed meat Proximates hydroxyproline RMLGC7140 Soft drink Colours RMLGC7105 Rice pudding Proximates elements RM

PurityLGC7300 Butylated hydroxytoluene (BHT) Purity CRMLGC7302 Saccharin Purity CRMLGC7011-15 Orange juice solutions Brix refractive index CRM

New reference materials


V A M N E W S


Pharmaceutical reference substances werefirst introduced in the 1950s by the

various pharmacopoeias as an integral partof the written monographs where it wasbelieved that direct comparison of sample

and standard would improve the quality ofthe measurement process In this respectthey were some of the first routinely usedreference materials

Since then the major pharmacopoeias

have issued many hundreds of pharma-ceutical reference substances and continueto do so at an ever-increasing rate Demandcontinues to increase driven by the universaladoption of product licensing and associatedquality systems and the increased use ofgeneric drugs

LGC have launched the first issue oftheir lsquoPharmaceutical reference substancesrsquocatalogue The aim of the catalogue is toassist the analytical community by providinga single source from where they canpurchase pharmaceutical referencesubstances The catalogue contains acomprehensive listing of over 3000reference substances from the followingpharmacopoeiasbull United States Pharmacopeia

and National Formularybull British Pharmacopoeiabull European Pharmacopoeiabull Pharmacopeacutee Franccedilaise bull WHO International Chemical Reference

Substances and SpectraLGCrsquos catalogue is unique in that the

catalogues of the above pharmacopoeia havebeen combined into a single listing andarranged in alphabetical order to make foreasy location and identification

The catalogue is available from LGCrsquosOffice of Reference Materials

Pharmaceutical referencesubstances

The formulation of the next VAMprogramme is well under way It is

being carried out by LGC and NPL onbehalf of the DTI Formulation of theprogramme was informed by a wideconsultation exercise to identify priorityareas both for the maintenance of existingcapability and for the development andvalidation of new techniques to meetupcoming measurement and analytical

challenges for the UK economy The PublicConsultation Documents describingproposals for the chemical biochemical andphysical parts of the programme werereleased in early January All commentsreceived will be reviewed and a Final Draftwill be submitted to DTI in March

The proposed VAM programme isfocused on the development of a practicalmeasurement system for the UK which is

firmly linked to the international one Theprogramme has the objective of ensuringthat the infrastructure is in place in the UKto enable valid measurements and analysesto provide quality data for industrygovernment and regulators As world tradeexpands the need to demonstrate thevalidity of analytical results is becomingmore critical It is also becoming apparentthat analytical measurements based on

VAM 2000 ndash 03

sound science are of growing importance forsettling trade conflicts and addressing safetyconcerns International efforts championedby the CCQM (a sub-group of theInternational Committee on Weights andMeasures the CIPM) are aiming to improvethe comparability of these measurements ona world-scale by establishing an infra-structure based on traceable measurementsOther drivers such as the continuing trendtowards performance based methods and thetype approval of analytical equipment andtest kits are also pushing in this direction

The chemical programme is focused onputting in place the tools and techniques toenable traceable measurements to be madein the UK The key elements of the proposedchemical programme arebull developing primary analytical methods

particularly those based on massspectrometry for more complexanalytical matrices

bull demonstrating the equivalence of theUK chemical measurement capabilitiesand reference values through theparticipation in key national andinternational studies

bull developing techniques for controlling measurement uncertaintyand matrix effects

bull producing Certified Reference Materialsthrough European collaboration anddeveloping ways of producing low costQC Laboratory Reference Materials

bull piloting elements of a new chemicalmeasurement infrastructure based ontraceable measurements

bull several knowledge transfer projectsincluding proposals for work to train

and assess analysts in the core analyticalcompetencies and provide coaching andadvice on common problem areas suchas cost effective method validation

the need to demonstrate the validity of analytical

results is becoming more critical

It is also proposed that a greater portionof effort be directed towards bioanalysisparticularly nucleic acid measurements andthe characterisation of bioparticulates Theproposals for the bioanalytical programmeinclude work aimed atbull pioneering the development of primary

methods for the quantitation of DNAand the evaluation of key amplification-based quantitation

bull finalising the development of a novelinternal control for DNA analysis andthe development of a reference systemfor characterising the size distributionand activity of bioaerosols

bull evaluating newly emerging DNAtechniques and developing protocols and reference standards to enable usersto check out the performance of the newtechnologies and be aware of theirstrengths and limitationsThe proposed physical programme is

targeted at the requirements for gas andparticulate measurements surface analysisand electrochemical methods Key elementsof the programme includebull work to support valid measurements

of gases and particulates important forindustrial processes vehicle and aircraft

emission and for air quality industrialand occupational exposure monitoring

bull development of generic techniques for the analysis of trace gases including water vapour at the parts per billion level

bull validation of novel optical and massspectrometric techniques now findingwider application for gas analysis

bull development of a calibration capabilityfor sensors used to measure HazardousAir Pollutants in the field

bull provision of new gas concentrationstandards for some important industrial and medical applications and for indoor air

bull development of calibration standards for pH and electrolytic conductivity

bull development of methods and provisionof data to validate surface analysistechniques This work builds onactivities in previous programmes whichis well advanced for simple molecules atsurfaces but must address fundamentalissues for larger molecules

bull development and validation oftechniques for the analysis of surfaces at nanometre resolution

bull knowledge transfer activities to maximisethe take-up of best measurementpractice and to ensure effective input of UK expertise and views into relevantinternational standardisation activitiesBuilding a practical system based on

traceable measurements will be a challengingtask However the proposed programme hasbeen designed such that the steps along theway will contribute to quality improvementsthroughout the system


V A M N E W S

The United Kingdom AccreditationService (UKAS) has been accrediting

laboratories for many years to therequirements of M10 the lsquoNAMASAccreditation Standardrsquo which incorporatedthe requirements of ISOIEC Guide 25 andEN45001 A new standard ISOIEC 17025lsquoGeneral Requirements for the Competence

of Testing and Calibration Laboratoriesrsquowas published by ISO in February 2000 andwill replace ISO Guide 25 The newstandard will be used by AccreditationBodies all over the world for the assessmentof competence of laboratories

The new standard is a comprehensiveexpression of the requirements that a

laboratory needs to meet in order todemonstrate that it is technically competentand operates a relevant recognised QualitySystem ISOIEC 17025 builds on thefoundations of the existing standards andtakes into account the operating experiencegained over the years since their publicationIn many areas existing practice is

New international standard forthe operation of laboratories


V A M N E W S

incorporated into the standard althoughthere are some differences

What are the main differences

The standard includes a section onmanagement requirements which ismodelled on ISO 90011994 but writtenspecifically for laboratory operations Someaspects of management system requirementsare described in more detail and have moreemphasis than seen in previous standardsThese aspects include the followingbull Review of requests tenders and contracts

(or contract review) This area was ratherweakly expressed in the previous standardsthere is now a more explicit statementthat the onus is on the laboratory toensure that the clientrsquos needs areidentified and that the proceduresselected meet those requirements

bull Document control A clearer expression of the requirements is given than seen in previous standards

bull Preventive action A more proactiveapproach will be required to identify

improvements and potential problemsbefore non-compliances are identifiedThe technical requirements in ISOIEC

17025 are similar to those detailed in M10and other ancillary UKAS publicationsHowever a significant addition to thestandard is the identification of therequirements for lsquoReporting opinions andinterpretationsrsquo This is a new area forUKAS as M10 specifically excluded thisaspect from accreditation As a resultUKAS is setting up a pilot study as part of adevelopment project in order to establish the principles for assessing this aspect of the standard

Another area that is given greateremphasis in the new standard is thelsquoSelection and use of methodsrsquo includingmore detailed requirements for thevalidation of both in-house developed andnon-standard methods

How does this affect UKASaccredited laboratories

UKAS will be able to assess and offeraccreditation to ISOIEC 17025 shortly after

publication and eventually M10 will bewithdrawn To allow time for existingaccredited laboratories to adapt to the newstandard a two year transition period will begiven during which time the M10 standardmay still be used Any potential applicantlaboratories should be addressing therequirements of ISO 17025 rather than M10as soon as possible after its publication

The advent of a single standard replacingISO Guide 25 EN45001 and eventuallyM10 will help to strengthen and extend theinternational recognition of calibration andtest results by providing a more level lsquoplayingfieldrsquo for laboratory operation

Copies of ISOIEC 17025 are availablefrom BSI

UKAS is recognised by Government as thesole national accreditation authority for theAccreditation of Calibration and TestingLaboratories Certification Bodies andInspection Bodies

Last July the CITAC Secretariat wastransferred from LGC to the Institute

of Reference Materials and Measurement(IRMM) in Belgium

Readers of VAM information willrecognise CITAC (Co-operation onInternational Traceability in AnalyticalChemistry) by the fact that it has producedguidelines on accreditation in chemicallaboratories1 research and development2 andmethod validation3 two of which were inconjunction with EURACHEM Howeversince its birth in 1993 CITAC has beenextremely active in the field of chemicalmeasurement comparability and traceabilityand has forged strong links with otherinternational organisations such as ISOILAC CCQM and AOAC

It could be argued that many of CITACrsquosactivities are similar to those in the VAMprogramme However with so many diverse

cultures worldwide an international forum isnecessary so that common issues can bediscussed and actioned globally The CITACWorking Group with a membership spanningthe Americas Europe (including the UK)Asia and Australia has taken on this role

Upon relinquishing responsibility for theCITAC Secretariat Dr Ron Walker said ldquoIthas been an honour and a privilege to havebeen associated with CITAC during the pastseven years The work of CITAC has beenof the highest quality and has contributedgreatly to moving on the debate about thekey issues of our time namely comparabilitytraceability and uncertainty I wish the newsecretary Dr Ioannis Papadakis everysuccess in carrying out what has been forme an enjoyable and informative taskrdquo

The new CITAC Secretariat is now fully operational For further informationcontact

The CITAC SecretariatJRC - IRMMB2440 GEELBELGIUMTel (32) 14 571 682

Fax (32) 14 571 863

Email citacjrcirmmbe

1 International Guide to Quality in

Analytical Chemistry An Aid to

Accreditation CITAC (CG1) 1995

2 Quality Assurance for Research and

Development and Non-Routine Analysis

EURACHEM CITAC (CG3) 1998

3 The Fitness for Purpose of Analytical

Methods A Laboratory Guide to

Method Validation and Related Topics


CITAC Secretariat moves to Belgium


V A M N E W S

V A M P R O D U C T S A N D S E R V I C E S

Over 300 metrologyinstrumenttestingtechnical staff and local authority

standards officers from across the countryhave registered interest in gaining nationalrecognition of their work competences byobtaining an NVQ through measurementtesting and calibration evidence routesThese evidence routes are part of theEMTA Awards Ltd Technical ServicesNVQSVQ

The Level 3 NVQ is composed of threemandatory units that assess an individualrsquoscompetences in a general workplaceengineering organisation A further two unitsare then required (optional units) which are

specific to the area of measurement andcalibration within which an individual works

In Autumn 1998 a consortium led byProfessor Barry Jones Director of the BrunelCentre for Manufacturing Metrology(BCMM) at Brunel University was awardeda DTI contract (as part of the NationalMeasurement Partnership Programme 1998-2001) to undertake the task of promotingthe NVQ with measurement evidence routesacross the country Underpinning materialsare being developed to cover subject basicsmechanical electricalelectronic physicaland analytical measurements Arrangementsare in hand for these materials to be printed

published and distributed by TrainingPublications Ltd (the wholly ownedsubsidiary of EMTA) Relevant assessorstraining workshops are being run

Further information is available fromCaryl Brown NVQ Project AdministratorBCMM Brunel University UxbridgeMiddlesex UB8 3PHTel 01895 203361Fax 01895 812556Email carylbrownbrunelacukWebsite wwwbrunelacukresearchbcmmmeasnvqhtm

Measurement testing andcalibration evidence routes for NVQsSVQs

The aim of the VAM programme is notonly to improve the quality of analytical

measurements but also to realise theeconomic benefits of such improvementsTo this end it is vital that progresscontinues to be made on achievinginternational harmonisation The benefits tothis approach are not only the direct onesconcerned with international trade but alsoless visible ones such as the value of sharingcosts between countries and using a widerpool of expertise through collaboration In

order to further such harmonisation LGChas signed a memorandum of collaborationwith two key European measurementinstitutesbull The Institute of Reference Materials

and Measurements (IRMM) TheIRMM based at Geel in Belgium is one of the European CommissionrsquosJoint Research Centres responsible for reference materials referenceanalytical measurements and neutrondata measurement

bull The Swedish National Testing andResearch Institute (SP) SP based atBorarings is the national institute fortechnical evaluation testingcertification metrology and research LGC will be working closely with both

IRMM and SP to improve comparability andtraceability of chemical measurementsCollaborative initiatives will cover a broadspectrum of chemical measurement issuessuch as chemical metrology certified referencematerials proficiency testing and training

International collaboration

L GC has been assisting in thepreparation of an European database of

Proficiency Testing schemes This wasscheduled to go live on 1 March 2000 It

includes chemical biological and physicalschemes but not clinical or metrologicalschemes and gives detailed information ofmethodology scope quality costs etc It may

be found on httpwwweptisbamde but ifanyone does not have internet access LGCrsquosProficiency Testing Advisory Service(PTAS) will be pleased to assist

Proficiency Testing




The pack lsquoBasic Laboratory Skillsrsquopublished by LGC aims to improve

the quality of analytical measurements madein the laboratory by introducing theprinciples of good practice The packcomprising a booklet - lsquoGuide to ImprovingAnalytical Quality in Chemistryrsquo and a CD-ROM - lsquoBasic Laboratory Skillsrsquo wasdeveloped by the education and training

team at LGC in conjunction with teachersand practitioners of analytical chemistry andwith support from the VAM programme

The guide is aimed at students (eg16ndash18) who have little practical experienceand have not had the opportunity to performpractical procedures on a regular basisFeedback has indicated that it is also of useto new employees starting work in a

traditional analytical laboratory at a juniorgrade work experience students in analyticallaboratories and first year university studentsin science departments where basiclaboratory skills are a requirement

The pack costs pound15 and can bepurchased from the VAM Helpdesk at LGC

Basic Laboratory Skills ndash a trainingpack for laboratory techniques

C H E M I C A L N O M E N C L A T U R E

The meaning of unitsKevinThurlow LGC

The dangers of ambiguity in chemical

nomenclature have been discussed in

previous issues of VAM Bulletin but little

attention has been paid to the correct use of

units There is no point carrying out lengthy

analytical procedures with expensive

equipment skilled analysts pure standards

suitable reference materials and accredited

methods if the published results do not

make senseThe International Organization for

Standardization (ISO) Systegraveme InternationaldrsquoUniteacutes (SI) and the International Union of

Pure and Applied Chemistryrsquos Inter-divisional Committee on Nomenclature andSymbols (IDCNS) have all published adviceon units They do not always agree but effortsare made to adopt a consistent approach

Problems start with the basic SI lsquoMKSrsquounits The metre and second are basic unitsbut there has been opposition to the use ofthe kilogram as the unit of mass because ithas a prefix There have been varioussuggestions to get round this problem likecalling the kilogram the lsquoGiorsquo after an Italianscientist called Giorgio So one gram (1g)would equal one milliGio (1mG) It wasdecided not to change to the Gio partlybecause there could be confusion betweenlsquogrsquo and lsquoGrsquo Since scientists often do thingslike this the average person in a supermarket

could be excused for doing the same Thesymbol for gravitational constant (G) wouldnot help Another suggestion was to uselsquoquilorsquo to mean one kilogram but this hasthe drawback that names beginning lsquoqursquorarely find favour internationally and areusually replaced with lsquokrsquo The prospect ofusing lsquokilokilorsquo instead of lsquomegagramrsquo wouldprobably be unappealing

The difference between upper and lowercase letters can cause difficulties There areonly limited possibilities for single letterprefixes even using the Greek alphabet aswell Therefore we have the unfortunatesituation where lsquomrsquo means lsquomillirsquo (10-3) andlsquoMrsquo means lsquomegarsquo (106) The SI prefixes1 areshown in Table 1

The prefixes towards the bottom of thetable are not used very often but IDCNS isseeking to expand the list to powers of 27and 30 Suggestions for names of theseprefixes are welcome The existing prefixesshould be printed upright (not in italics)and in the appropriate case It is surprisinghow often even the common prefixes aremangled People wrongly use lsquoKrsquo for lsquokilorsquoand even lsquohrsquo for lsquonanorsquo This is a very goodway to confuse other people Prefixes mustbe used individually so you would say lsquoMgrsquonot lsquokkgrsquo It could be even worse if someoneused lsquoppmrsquo instead of lsquoymrsquo

This leads us to the problem of very

Sub-multiple Prefix Symbol Multiple Prefix Symbol

10-1 deci d 10 deca da

10-2 centi c 102 hecto h

10-3 milli m 103 kilo k

10-6 micro micro 106 mega M

10-9 nano n 109 giga G

10-12 pico p 1012 tera T

10-15 femto f 1015 peta P

10-18 atto a 1018 exa E

10-21 zepto z 1021 zetta Z

10-24 yocto y 1024 yotta Y

Table 1



frequently seen units like ppm ppb and What do these actually mean These are notSI recommendations and ISO say theyshould not be used Commonly usedconcentration units (like and ppm) areoften quoted without saying whether theauthor is using (eg) mass fraction molefraction or volume fraction The meaning oflsquo10 sodium chloridersquo solution may seemclear enough as the sodium chloride is solidand the waterrsquos density of roughly 1gcm-3

means you can use mass or volume withoutchanging the overall value much Howeversuppose we have lsquo10 pyridine in ethanolrsquoThese are both liquids and densityconsiderations mean that you have to statefor example lsquomass fraction is 10rsquo Unitslike lsquo mmrsquo are not recommended It istherefore far easier and also clearer to saylsquo10 g100 grsquo The same applies to lsquoparts permillionrsquo (ppm) It makes sense to use 37mgkg (or mgkg-1) to avoid ambiguity

There are worse examples for examplelsquoppbrsquo This is based on the American billion(109) rather than the original billion (1012)Similarly lsquopptrsquo is used for lsquoparts per trillionrsquo

based on the American trillion (1012) ratherthan the original trillion (1018) To makematters worse some authors have used lsquopptrsquoto mean parts per thousand Readers may bepleased to know that the litre is still goingstrong and the prefixes lsquolrsquo and lsquoLrsquo are bothpermitted The latter is preferred as lsquo1Lrsquo isclearer than lsquo1lrsquo

The world of computers brings its ownproblems Many years ago computerworkers decided that as 210 is nearly thesame as 1000 the SI prefix lsquokilorsquo could beused for 1024 As time passed more peopleused computers and some of those peopleknew lsquokilorsquo meant 1000 not 1024 Otherpeople lsquoknewrsquo lsquokilorsquo meant 1024 in this caseThen computers got bigger Megabytesarrived But what was a megabyte Some manufacturers thought it was 220 = 1 048 576 bytes others thought it was 1 024 000 (1000 x 210) and others thoughtit was 1 000 000 That is three definitions ofone unit Now we talk about gigabytesterabytes etc the errors grow and grow TheInternational Electrotechnical Commission(IEC) has announced some clarifying

prefixes based on SI units They give lsquokibirsquo(to mean lsquokilobinaryrsquo) as prefix for 210 lsquomebirsquo(meaning lsquomegabinaryrsquo) as prefix for 220 etcSo one mebibyte (1 MiB) = 220B and onemegabyte (1 MB) is 106B This restores theSI units to their correct usage and introducesa logical and easily understood extension tothe system For anyone eager to use thissystem lsquomebirsquo is pronounced first syllable asin its analogue lsquomegarsquo second syllable lsquobeersquoThis applies to the other prefixes lsquogibirsquo lsquotebirsquolsquopebirsquo and lsquoexbirsquo Presumably lsquozebirsquo and lsquoyobirsquoare just round the corner

Who would think something as simple asa unit could cause so many problems

If you are having problems withchemical nomenclature we are able to offeradvice (see back cover for details)

REFERENCES

1 Quantit ies Units and Symbols in

Physical Chemistry Ian Mills et al for

IUPAC (Blackwell Scientific)

F O R T H C O M I N G E V E N T S

Analytica 2000

11ndash14 AprilMunich Germany

Analytica 2000 is the largest Europeantrade fair for the life sciences laboratory andindustrial applications Some of the worldrsquosleading companies present progressive analysistechniques for the life sciences new solutionsfor the laboratory medical laboratorydiagnostics and industrial applications forchemistry pharmaceuticals measurementtesting and control technology

At the same time the Analyticaconference presents top internationalresearch

For further information please contactMesse Muumlnchen GmbHMessegelaumlndeD-81823 MuumlnchenGermanyTel (49) 89 949 20380Fax (49) 89 949 20389Email infoanalyticadeWeb httpwwwanalyticade

2000 Annual Conference

16ndash20 AprilUMIST Manchester

The second RSC Annual Conferencewill take place at UMIST and theBridgewater Hall in Manchester Theconference is not intended to duplicatespecialist meetings but rather to attempt toportray chemistry from the widest possibleperspective in a way which is relevant to all

RSC members to promote collaborationand encourage new areas of researchspanning the classical divisions of chemistry

The conference will look at several keydevelopments in the molecular sciences inrecent years including exploring chemistryat the interface with biology developingclean and sustainable processes to reduce theenvironmental impact of our industry andthe quest for nanoscale devices

For further information please contactNicole MorganConferences DepartmentRoyal Society of ChemistryBurlington HouseLondon W1V 0BNTel 020 7437 8656Fax 020 7734 1227Email conferencesrscorg

Forthcoming events



International conference on metrology ndash

Trends and applications in calibration and

testing laboratories

16ndash18 May Jerusalem Israel

The meeting is organised by theNational Conference of StandardLaboratories (NCSL) Co-operation forInternational Traceability in AnalyticalChemistry (CITAC) and the IsraeliMetrological Society The conference willdiscuss metrology new measurementmethods and instruments interlaboratorycomparisons proficiency testingtraceability ethical problems in metrologyand education in the third millennium

For further information please contactDr Henry HorowitzConference SecretariatISAS International SeminarsPO Box 34001Jerusalem 91340IsraelTel (972) 2 6520574Fax (972) 2 6520558Email isasnetvisionnetil

ACHEMA 2000

22ndash27 May Frankfurt Germany

ACHEMA 2000 is an internationalmeeting on chemical engineering environ-mental protection and biotechnology Withalmost 4000 exhibitors from all over theworld ACHEMA will present future trendsin the process industries In addition to thewell-established exhibition groups there is anew exhibition group on Biotechnologywhich includes a presentation of biotech-nology products and processes

A special show on Synthesis Screeningand Sequencing equipment reflects thecurrent developments in the field ofcombinatorial chemistry concurrent analysisand test methods The show will beaccompanied by an international symposium

For further information please contactDECHEMA eVTheodor-Heuss-Allee 25D-60486 FrankfurtGermanyTel (49) 69 75640Fax (49) 69 7564201Web httpwwwdechemade

3rd Workshop on proficiency testing

in analytical chemistrymicrobiology and

laboratory medicine

24ndash26 SeptemberBorarings Gothenburg Sweden

A workshop on current status problemsand future direction of proficiency testing inanalytical chemistry microbiology andlaboratory medicine organised jointly byEURACHEM and EQALM A trainingcourse will be held on 24 September withthe EURACHEM Executive meeting on 27September

Lectures and working groups willhighlight international harmonisation ofPTEQA schemes the use of PT in theaccreditation process implementation of theuncertainty concept into PTEQA schemesand accreditation of PTEQA schemes

For more information please contactUlf OumlrnemarkSP Swedish National Testing and Research InstitutePO Box 857SE-501 15 BoraringsSwedenTel (46) 33 165275Fax (46) 33 123749Email ulfornemarkspse

W E B L I N K S

Useful web linksThe Analytical Chemistry Springboard

httpwwwanachemumusejumpstationhtm

This provides a comprehensive list ofanalytical chemistry resources on theInternet It covers a wide range of techniquesand subjects such as standardisation theuse of reference materials and best laboratorypractice Links to other organisationsinternet newsgroups and suppliers are also given

Rolf Claessenrsquos Chemistry Index

httpwwwclaessennetchemistry

This site is one of the more well knownvirtual libraries for chemistry giving accessto a wide range of resources includingjournals patents databases and companiesThere is a specific section dedicated tospectroscopy and chromatography

Royal Society of Chemistry

httpwwwrscorg

The RSC have many resources availableon their website There is access to theLibrary Catalogue (the collection is housedat Burlington House in London) and afacility to search their on-line electronicjournals Of particular interest is the abilityto search the Analytical Abstracts databasefor free (coverage 1980 to date) However a subscription is required to access fullinformation on the database


W E B L I N K S

The NIST Chemical Science andTechnology Laboratory

httpwwwcstlnistgov

The work of NIST in the following areasare covered analytical chemistry biotech-ology physical and chemical propertiesprocess measurement and surface andmicroanalysis science

NIST WebBook

httpwebbooknistgov

The WebBook provides a gateway to thedata collections of the National Institute ofStandards and Technology as well as thestandard reference materials catalogue TheChemistry WebBook gives thermochemicaland spectral information on a number ofchemicals

Scimedia

httpwwwscimediacom

The Science Hypermedia website givesaccess to its Encyclopedia of AnalyticalInstrumentation and a basic tutorial coursecovering the basics of analytical chemistry

Newsgroups

httpwwwnewsscichemanalytical

The analytical chemistry USENETdiscussion group Topics range from basicchemistry to information sources toequipment to detailed analytical problems

VAM Helpdesk020 8943 7393

VAM advisory services

Reference materials advisory service(REMAS)Kevin Thurlow LGC020 8943 7424

Analytical QA advisory serviceDavid Holcombe LGC020 8943 7613

Proficiency testing advisory serviceKevin Thurlow LGC020 8943 7424

Gas analysis advisory serviceDr Paul Quincey NPL020 8943 6788

Chemical nomenclature advisory service(CNAS)Kevin Thurlow LGC020 8943 7424

Statistics HelplineVicki Barwick LGC020 8943 7421

LGCQueens RoadTeddingtonMiddlesex TW11 0LYTel 020 8943 7000 (switchboard) Fax 020 8943 2767Web httpwwwlgccouk

httpwwwvamorguk

National Physical Laboratory (NPL)Queens RoadTeddingtonMiddlesex TW11 0LWTel 020 8977 3222 (switchboard)

020 8943 6880 (NPL Helpline)Fax 020 8943 6458Web httpwwwnplcouk

Aerosol Science CentreAEA Technology plcE6 Culham AbingdonOxfordshire OX14 3EDTel 01235 463677Fax 01235 463205Email aerosolsaeatcouk

Produced by Horrex Davis Design Associates 300

C O N T A C T S

Contact points

Traceable measurement A different route to reliable analytical data


VAM and the measurement issues related to QUID

The reliability of mass spec for identification purposes


Spectra in quantitative chemical analysis 1 Smoothing to reduce noise


Resource for Quality Assurance of chemical measurements


Pharmaceutical reference substances

VAM 2000-03

New international standard for the operation of laboratories


Measurement testing and calibration evidence routes for NVQsSVQs


Proficiency Testing

Basic Laboratory Skills - a training pack for laboratory techniques

The meaning of units

Forthcoming events

Useful web links

Contact points

Contents


C O N T E N T S

Cover photograph by Andrew Brookes

Alison GillespieKeith MarshallEditors

General enquiries about VAM toVAM Helpdesk 020 8943 7393vamlgccouk

LGCrsquos addressLGCQueens RoadTeddingtonMiddlesex TW11 0LY

The DTI VAM programme

The DTIrsquos programme on ValidAnalytical Measurement (VAM) is anintegral part of the UK NationalMeasurement System The VAMprogramme aims to help analyticallaboratories demonstrate the validity oftheir data and to facilitate mutualrecognition of the results of analyticalmeasurements

The VAM programme sets out thefollowing six principles of good analyticalpractice backed up by technical supportand management guidance to enablelaboratories to deliver reliable resultsconsistently and thereby improveperformance

1 Analytical measurements should bemade to satisfy an agreed requirement

2 Analytical measurements should bemade using methods and equipmentwhich have been tested to ensure theyare fit for their purpose

3 Staff making analytical measurementsshould be both qualified and competentto undertake the task

4 There should be a regular independentassessment of the technical performanceof a laboratory

5 Analytical measurements made in onelocation should be consistent with thoseelsewhere

6 Organisations making analyticalmeasurements should have well definedquality control and quality assuranceprocedures

Editorial

Traceable measurements A different route to reliable analytical data 3

Guest column

Methods for testing Escherichia coli 5

Focus on sectors

VAM and the measurement issues related to QUID7

Contributed articles

The reliability of mass spec for identification purposes 12

Ultrafine particles and air quality control14

Spectra in quantitative chemical analysis I Smoothing to reduce noise 18

Case study

Titanium dioxide manufacture A microcosm of analytical best practice 23

VAM in education

Resource for Quality Assurance of chemical measurements 27

Reference materials update 28

VAM news

VAM 2000ndash03 29

New international standard for the operation of laboratories30

CITAC Secretariat moves to Belgium 31

Measurement testing and calibration evidence routes for NVQsSVQs32

International collaboration32

VAM products and services 32

Chemical nomenclature

The meaning of units33

Forthcoming events34

Web links 35

Contact points 36



E D I T O R I A L

Mike SargentLGC




















REFERENCES






Directorate by LGC)




2ndash4 1999









Spring 1999












17 13-15 Autumn1997





E D I T O R I A L










illness and disease

































NT ndash Not tested







isolation medium



CTSMACg very good

SMACh poor

SMAC + 13 CTi poor

SMAC + 23 CTj poor


SD-39l ndash







REFERENCES














424ndash427 1994











London 1999


Introduction


















































Figure 1
















































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points



E D I T O R I A L

Mike SargentLGC




















REFERENCES






Directorate by LGC)




2ndash4 1999









Spring 1999












17 13-15 Autumn1997





E D I T O R I A L










illness and disease

































NT ndash Not tested







isolation medium



CTSMACg very good

SMACh poor

SMAC + 13 CTi poor

SMAC + 23 CTj poor


SD-39l ndash







REFERENCES














424ndash427 1994











London 1999


Introduction


















































Figure 1
















































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points









REFERENCES






Directorate by LGC)




2ndash4 1999









Spring 1999












17 13-15 Autumn1997





E D I T O R I A L










illness and disease

































NT ndash Not tested







isolation medium



CTSMACg very good

SMACh poor

SMAC + 13 CTi poor

SMAC + 23 CTj poor


SD-39l ndash







REFERENCES














424ndash427 1994











London 1999


Introduction


















































Figure 1
















































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points










illness and disease

































NT ndash Not tested







isolation medium



CTSMACg very good

SMACh poor

SMAC + 13 CTi poor

SMAC + 23 CTj poor


SD-39l ndash







REFERENCES














424ndash427 1994











London 1999


Introduction


















































Figure 1
















































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points



























NT ndash Not tested







isolation medium



CTSMACg very good

SMACh poor

SMAC + 13 CTi poor

SMAC + 23 CTj poor


SD-39l ndash







REFERENCES














424ndash427 1994











London 1999


Introduction


















































Figure 1
















































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points





REFERENCES














424ndash427 1994











London 1999


Introduction


















































Figure 1
















































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points











































Figure 1
















































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points













































































the analyte


this standard

Enforcement of QUID





REFERENCES










SI 19961499























































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points





















































described above




















Masses monitored


330 1-100 1922

330 1-100 173 1-100 816

330 1-100 173 1-100 125 1-100 128

330 1-40 1753

330 1-40 173 1-100 735

330 1-40 173 1-100 125 1-100 111

330 1-40 173 60-100 10

330 1-40 173 60-100 125 60-100 1





Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points




Conclusions



REFERENCES



72487ndash490 1989


(1993)







61 1247ndash1252 1978











GC-MS (1998)







David Booker

AEA Technology

Environment
































Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points


























Why particles












of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points







of new legislation










































































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points
































bull hellipetc

OUTPUTS

BENEFITS



Measurement







Measurement






bull QAhellipetc




bull hellipetc





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points





REFERENCES











HMSO London 1995










1996



Unit VAM programme





AEA-TSD-0766 1995



PeterCumpsonNPL

Introduction








Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points


Why smooth











When not to smooth














































































































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points




























































































a polynomial

Gaussian smoothing






























conclude










energy resolutions


































by Wertheim13



































smoothing method

Conclusions



























REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points



REFERENCES



1992








21 351ndash363 1988


Chem 36 1627 1964


Anal Chem 44 1906 1972







Chem 53 1583ndash1586 1981


1981




Press 1986




New York Dover 1979


239ndash251 1975


Chem 52 2315ndash2321 1980



C A S E S T U D Y




Summary


















Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points



Introduction






C A S E S T U D Y

















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points
















C A S E S T U D Y









Opacity

Gloss






























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points





























of manufacture

Proficiency testing




Reference materials
















































C A S E S T U D Y














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points














of the product


























this case)











analytical science

C A S E S T U D Y

































tertiary education





















analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points










analytical science


































V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points


V A M N E W S


















VAM 2000 ndash 03





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points





























V A M N E W S








V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points


V A M N E W S
























Fax (32) 14 571 863














V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points


V A M N E W S





















Proficiency Testing






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points






































10-18 atto a 1018 exa E



Table 1











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points











REFERENCES





Analytica 2000











Forthcoming events









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points









ACHEMA 2000







laboratory medicine





W E B L I N K S








httpwwwrscorg



W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points


W E B L I N K S


httpwwwcstlnistgov


NIST WebBook

httpwebbooknistgov


Scimedia

httpwwwscimediacom


Newsgroups












httpwwwvamorguk





C O N T A C T S

Contact points











VAM 2000-03





Proficiency Testing



Forthcoming events

Useful web links

Contact points