RESIDUE ANALYSIS OF 500 HIGH PRIORITY PESTICIDES:BETTER BY GC–MS OR LC–MS/MS?

Lutz Alder,1* Kerstin Greulich,1 Gunther Kempe,2 and Barbel Vieth1

1Federal Institute for Risk Assessment, Residue Analysis Unit,Thielallee 88-92, 14195 Berlin, Germany2Landesuntersuchungsanstalt fur das Gesundheits- und Veterinarwesen,Standort Chemnitz, Zschopauer Street 87, D-09111 Chemnitz, Germany

Received 10 October 2005; received (revised) 25 January 2006; accepted 28 January 2006

Published online 3 June 2006 in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/mas.20091

This overview evaluates the capabilities of mass spectrometry(MS) in combination with gas chromatography (GC) and liquidchromatography (LC) for the determination of a multitude ofpesticides. The selection of pesticides for this assessment isbased on the status of production, the existence of regulationson maximum residue levels in food, and the frequency ofresidue detection. GC–MS with electron impact (EI) ionizationand the combination of LC with tandem mass spectrometers(LC–MS/MS) using electrospray ionization (ESI) are identifiedas techniques most often applied in multi-residue methods forpesticides at present. Therefore, applicability and sensitivityobtained with GC–EI–MS and LC–ESI–MS/MS is individu-ally compared for each of the selected pesticides. Only for onesubstance class only, the organochlorine pesticides, GC-MSachieves better performance. For all other classes of pesticides,the assessment shows a wider scope and better sensitivity ifdetection is based on LC–MS. # 2006 Wiley Periodicals, Inc.,Mass Spec Rev 25:838–865, 2006Keywords: tandem mass spectrometry; gas chromatography;liquid chromatography; electron impact ionization; electro-spray ionization; multi-residue method; carbamates; organo-chlorine pesticides; organophosphorus pesticides; pyrethroids;sulfonylureas; triazines; triazoles; ureas; food; environmentalsamples

I. INTRODUCTION

Pesticides have been widely used throughout the world since themiddle of the 20th century. Based on the compilation of theBritish Crop Protection Council, approximately 860 activesubstances are formulated in pesticide products currently(Tomlin, 2003). These substances belong to more than 100substance classes. Benzoylureas, carbamates, organophosphor-ous compounds, pyrethroids, sulfonylureas, or triazines are themost important groups. The chemical and physical propertiesof pesticides may differ considerably. There are severalacidic pesticides; others are neutral or basic. Some compoundscontain halogens, others phosphorous, sulfur, or nitrogen. Theseheteroatoms may have relevance for the detection of pesticides. A

number of compounds are very volatile, but several do notevaporate at all. This diversity causes serious problems in thedevelopment of a ‘‘universal’’ residue analytical method, whichshould have the widest scope possible.

But such multi-residue methods are urgently needed.Probably, no other use of chemicals is regulated more extensivelythan that of pesticides. Maximum residue levels (or tolerances)have been established for pesticides in foodstuffs and drinkingwater in most countries to avoid any adverse impact on publichealth, and to insist on good agricultural practice. Residuesof systemic herbicides in soil used in the previous seasonmay influence the growing of succeeding crops. Residues ofinsecticides in surface water may cause adverse effects on aquaticorganisms. For these reasons a large number of laboratoriesare involved in the surveillance of maximum residue levels or inthe identification and quantification of pesticide residues inenvironmental matrices. In this context the use of numeroussingle-residue methods is usually too expensive. It has to be notedthat every company which applies for registration of a newpesticide has to provide residue analytical information. At least inthe EU, this part of a registration package is not confidential.

Depending on the purpose, determination of pesticideresidues may be target analysis or non-target analysis. Anexample of target analysis is the inspection of MRLs in food. Therelevant analytes are fixed by the residue definition given in theMRL regulation. These residue definitions may include relevantmetabolites or degradation products of the pesticides. In contrast,the EU regulation of residues in drinking water does not containdetailed residue definitions. Furthermore, residues in soil orsurface water are not regulated at all. In such cases, metabolites ordegradation products may be unknown. Their detection andidentification is part of the analytical task. Both types of analysishave the need for different analytical schemes and may requiredifferent instrumentation. In this review, we want to focus on theapplication of mass spectrometry (MS) in target analysis.

In the past decades, the methods for trace level determina-tion of pesticides have changed considerably. Since the early1970s most routine pesticide residue analysis has been conductedby gas chromatography (GC) in combination with electroncapture, nitrogen-phosphorous, and/or flame photometric detec-tion. Confirmation of results required the use of a further gaschromatograph equipped with a different type of column ordetector. Nowadays, using GC combined with MS, simultaneousdetermination and confirmation of pesticide residues can beobtained with one instrument in one analytical run. In most cases,

Mass Spectrometry Reviews, 2006, 25, 838– 865# 2006 by Wiley Periodicals, Inc.

————*Correspondence to: Dr. Lutz Alder, Federal Institute for Risk

Assessment, Fachgruppe 67, Thielallee 88-92, 14195 Berlin, Germany.

E-mail: l.alder@bfr.bund.de

the sensitivity obtained with GC–MS is similar to that ofclassical GC detectors. Selectivity of GC–MS can be adjusted bythe selection of appropriate molecular and fragment ions to avoidinterferences from co-extracted sample materials. Therefore, theimportance of GC with ECD, NPD, or FPD detection hasdecreased in pesticide residue laboratories.

Methods based on liquid chromatography (LC) were appliedmore rarely in the past, because traditional UV, diode array, andfluorescence detectors are often less selective and sensitive thanGC instruments. But in the last few years, the commercialavailability of atmospheric pressure ionization caused a specta-cular change. Compared to traditional detectors, electrospray(ESI) or atmospheric pressure chemical ionization (APCI) incombination with MS instruments have increased the sensitivityof LC detection by several orders of magnitude. Moreover, HPLCcolumn switching techniques and extensive sample cleanupprocedures become unnecessary if tandem mass spectrometersare used and operated in the selected reaction mode (SRM) (Stoutet al., 1998; Hernandez, Sancho, & Pozo, 2005). Due to thesuppression of most interfering signals by LC–MS/MS in theSRM, the signal-to-noise ratio increases distinctly and the fullsensitivity range of LC–MS instruments can be utilized.

The applicability of GC–MS in pesticide residue analysis issummarized in pesticide analytical manuals (Thier & Zeumer,1992; van Zoonen, 1998), applications from instrument produ-cers (Agilent Technologies, 1999), or scientific studies (Cairnset al., 1993; Fillion, Sauve, & Selwyn, 2000; Wong et al., 2003).Several mass spectral databases contain electron impact (EI)mass spectra of many pesticides (Ehrenstorfer, 2005; NIST/EPA/NIH, 2005). Analogous presentations of the scope of LC–MS/MS in the area of pesticide residue analysis are missing. Up tonow, the largest overview has been given by Lehotay et al. (2005),who applied LC–MS/MS for the determination of 144 pesticides.But a complete inventory of all available LC–MS/MS informa-tion does not exist.

Therefore, the aim of this review is to summarize all typicalprecursor and product ions appropriate for LC–ESI–MS/MSdetermination of 500 pre-selected pesticides (if these pesticidesare adequately ionized by electrospray) and the sensitivityobtained. The applicability of GC–MS with EI MS is checkedfor the same list of pesticides. Typical fragment ions areprovided, if their determination is possible. The decision betweentwo alternatives of quantitative determination also depends onsensitivity. For this reason, the smallest analyte concentrationrequired for GC–MS and/or LC–MS/MS is listed in addition.Finally, the achievable scope of multi-residue methods based onGC–MS or LC–MS/MS is presented.

II. SELECTION OF PESTICIDESFOR THIS COMPARISON

As noted above, approximately 860 active substances arecurrently used in pesticide formulations (Tomlin, 2003). Inaddition, several metabolites, degradation products, and ‘‘old’’(persistent) pesticides have to be considered by pesticide residueanalysts. Probably no technique is able to analyze all these >900analytes completely.

For this reason, a selection of ‘‘important’’ pesticides wasnecessary. The selection was started with the exclusion of >140pesticides, which are not important for the comparison of GC–MS versus LC–MS/MS. These pesticides are:

. Nine dithiocarbamates, 48 biological agents (bacteria,fungi, viruses, etc.), and 29 inorganic compounds, whichcannot be analyzed by multi-residue methods based on GC–MS or LC–MS/MS.

. Thirty-five pheromones, which are less important becauseresidues are not expected.

. Several isomers (e.g., alpha-cypermethrin, beta-cyperme-thrin, theta-cypermethrin, and zeta-cypermethrin), if one ofthese isomers is considered.

The following criteria were taken into account to select themore important substances from the remaining pesticides:

(1) Status of production: Selected pesticide should be listed inthat part of the 13th edition of the Pesticide Manual thatcontains the actually produced pesticides.

(2) Status of residue regulation in the EU or in Germany(which are completely available for us). Regulatedpesticides are preferred.

(3) Occurrence of residues: Those pesticides are preferred,which are more often found in food monitoring programs.

(4) Inclusion of important metabolites: Metabolites and/ordegradation products, which are included in the residuedefinition, should be considered in addition.

(5) At least one of both detection techniques (GC–MS or LC–MS/MS) must be applicable.

Using these criteria, 422 pesticides and 42 importantmetabolites were chosen. In addition, 36 pesticides wereselected, because their residues in food are regulated, eventhough these compounds are not produced any longer. Theresulting total number of 500 compounds is presented inTable 1. The compilation contains 81 organophosphoruspesticides, 43 carbamates, 40 organochlorines, 26 sulfonylur-eas, 24 triazoles, 23 triazines, 22 other ureas, 19 pyrethroids, 12aryloxyphenoxypropionates, and 10 aryloxyalkanoic acids. Inthe Pesticide Manual, the remaining 207 compounds are assig-ned to further 90 chemical classes.

The placement of some compounds into categories issomewhat arbitrary because some pesticides contain several ormore characteristic structural features. If the mode of action isconsidered, 172 herbicides, 171 insecticides, 105 fungicides,and 52 pesticides from other pesticide types (acaricides,bactericides, herbicide safeners, molluscicides, nematicides,plant growth regulators, and synergists) are selected. Approxi-mately 90% of those pesticides that are regulated by the EUCommission are included in the table. It should be noted that themajority of the excluded pesticides belongs to the group ofherbicides, which typically causes lower amounts of residues infood.

By selection of such a large number of pesticides, we triedto include most analytes being important in pesticide residueanalysis. But without a doubt, every selection must beincomplete. Several metabolites may be missing, as well as

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TABLE 1. Typical ions selected for GC-EI-MS or transitions used in LC-ESI-MS/MS and the sensitivity obtained with

both techniques

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some pesticides, which are important for other reasons notconsidered here. Nevertheless, this selection was not put togetherto promote a particular analytical technique.

III. SELECTION OF INSTRUMENTS ANDIONIZATION TECHNIQUES

The choice of the most appropriate instruments to handle themajority of samples and analytes is one of the most importantdecisions on investments in residue analytical laboratories. Thesame decision was necessary for the comparison presented here.

A. GC–MS

Ionization of pesticides in GC–MS can be done by EI, andpositive or negative chemical ionization (PCI, NCI). For ionseparation, single quad instruments are used most frequently.Additionally, GC–MS systems with quadrupole ion traps, time-of-flight (TOF) mass spectrometers or tandem mass spectro-meters are available.

Most of the published studies on residue analysis by GC–MS report on results obtained by single quadrupole instrumentsand EI ionization. Advantages of EI ionization are a low influenceof molecular structure on response, and a large number ofcharacteristic fragments. Extensive studies describe the simulta-neous determination of 245–400 pesticides by GC–EI–MS withsingle quadrupole mass filters (Cairns et al., 1993; Fillion, Sauve,& Selwyn, 2000; Stan, 2000; Chu, Hu, & Yao, 2005). The use ofion traps in scan mode is more simple because no selection ofcharacteristic ions is necessary during data acquisition. In fullscan mode these instruments are quite sensitive, and confirmationby library search is possible at lower concentrations. But,

compared to single quad instruments running in selected ionmonitoring mode (SIM), identical pesticides are covered and thesensitivity do not differ significantly (Cairns et al., 1993).

Chemical ionization is used more rarely. Positive or negativeCI–MS give better selectivity for several pesticides compared toEI. This results in chromatograms with reduced matrixinterference (Hernando et al., 2001). But the signal intensity ofdifferent pesticides (if identical amounts are injected) variesmuch more compared to EI ionization. Preferentially, GC–MSwith chemical ionization is focused on special substance classesonly, for example, organohalogen pesticides (Artigas, Martinez,& Gelpi, 1988; Chaler et al., 1998), pyrethroids (Ramesh &Ravi, 2004), and organophosphates (Russo, Campanella, &Avino, 2002). It is rarely used in multi-residue methods, becauseit is not a universal ionization technique. Finally, mass spectraproduced by chemical ionization usually contain a smallernumber of fragments, thus offering less information.

Available GC–TOF instruments can be operated in twodifferent modes. One type offers very high scan rates, allowingthe separation of overlapping peaks by automated mass spectraldeconvolution of overlapping signals (de Koning et al., 2003;Patel et al., 2004). This can result in up to 30,000 peaks fromcigarette smoke (Dalluge et al., 2002). Another type of GC–TOFinstruments offers high mass resolution, allowing data evaluationwith a narrow mass window of 0.02 Da (Cajka & Hajslova, 2004).However, most TOF instruments suffer from a reduced dynamicrange (Dalluge, Roose, & Brinkman, 2002). For this review, nosufficient information on multi-analyte GC–TOF was available.

In analogy to CI–MS and GC–TOF, a good suppression ofmatrix background is obtained by GC–MS/MS systems(Goncalves & Alpendurada, 2004). Even with extracts oftobacco, excellent selectivity and sensitivity were observed(Haib, Hofer, & Renaud, 2003). MS/MS experiments can beperformed using ion trap (Gamon et al., 2001; Aguera et al.,

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aEU regulation can be found on the websites: http://europe.eu.int/eur-lex/en/search/search_lif.html or http://europe.eu.int/eur-

lex/lex/en/repert/035020.htmb[MþNH4]þ used as quasimolecular ion.cRegulated metabolite in the EU.dAnalyte requires special HPLC conditions for detection with ESI–MS/MS.eQuasimolecular ion was [M–OH]þ.fReference 2 does not report the product ion.gQuasimolecular ion was [(M–O)/2]þ.hQuantitative degradation of the pesticide occurs in the GC injector.iReference 1 does not report the product ion.

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2002; Martinez Vidal, Arrebola, & Mateu-Sanchez, 2002) andtriple quadrupole mass analyzers (Leandro, Fussell, & Keely,2005). Some limitations in GC–MS/MS arise from the absenceof a universal soft ionization mode, which could be used for theefficient production of molecular ions of most pesticide classes.Chemical ionization generates high-intensity ions of only somepesticides classes. EI ionization is more universal, but often thetotal ion current is spread on many fragments, resulting in a lowintensity of parent ions of MS/MS experiments. Up to now, theprospects of GC–MS/MS are not totally clear. GC–MS/MSacquisition parameters are published for a small percentage ofselected pesticides. Therefore, it is too early to choose GC–MS/MS instead of GC—MS for a comparison with the mostappropriate LC–MS(/MS) approach.

B. LC–MS

If pesticides are not amenable to GC, the application of LC is thebest alternative. Likewise, LC may be combined with singlequadrupole instruments, quadrupole ion traps, triple quadrupole(tandem) mass spectrometers, TOF spectrometers, or hybridquadrupole TOF instruments.

In contrast to GC–MS, single quadrupole mass spectrometersare not used in the majority of recent studies dealing with LC–MS.A disadvantage of single quadrupole instruments (and ion trapsoperated in the SIM mode) is the high intensity of backgroundsignals produced from sample matrix and HPLC solvent clusters.Due to this chemical noise in real samples very low limits ofquantification cannot be achieved, even if the sensitivity of theseinstruments is high (Hernandez, Sancho, & Pozo, 2005).

The chemical background can be reduced significantly iftandem MS in combination with selected reaction monitoring(SRM) is applied. Even if a co-extracted matrix component has themolecular mass of a pesticide, usually both isobaric ions can beseparated in SRM experiments, because their fragmentation in thecollision cell most often results in different product ions. Therefore,tandem mass spectrometers offer excellent sensitivity and unsur-passed selectivity. For this reason, triple quadrupole mass analyzershave been the most often applied MS detectors until now (Pico,Blasco, & Font, 2004). Quadrupole ion traps may also be operated inthe MS/MS mode, which reduces the background to a level knownfrom tandem mass spectrometers. However, ion collection,fragmentation, and mass analysis of fragments is a step by stepprocess in traps and requires much more time than in triplequadrupole instruments, which do this in parallel. Furthermore, iontraps suffer from a limited dynamic range, a smaller potential tofragment very stable ions and the inefficiency to trap low massfragments (Pico, Blasco, & Font, 2004).

Time-of-flight mass spectrometers in combination with LCare more often used in high-resolution mode (typical masserror <2 mDa), which provides better discrimination of back-ground (Hogenboom et al., 1999; Ferrer et al., 2005). The mainadvantage of this type of instrument is the identification ofunknown peaks in a sample even if analytical standards arenot available (Garcia-Reyes et al., 2005; Thurman, Ferrer, &Fernandez-Alba, 2005). But, this advantage is usually not neededin the enforcement of maximum residue levels. Furthermore,identification of pesticides in samples is less certain by LC–

TOF–MS than identification of pesticides by GC–EI–MS(Maizels & Budde, 2001).

The use of a hybrid quadrupole time-of-flight instrument(Q–TOF) allows the most certain confirmation. This confidenceis based on the combination of retention time, mass of the quasimolecular ion selected by the quadrupole mass filter, and thecomplete collision induced mass spectrum obtained by the TOFanalyzer (Hernandez et al., 2004). Unfortunately, the sensitivityof Q–TOF instruments in relation to triple quadrupole analyzersis one order of magnitude lower (Hernandez et al., 2004; Nunez,Moyano, & Galceran, 2004). Additionally to this drawback, asmaller linear range restricts the use of Q–TOF for thequantification of residues.

All LC–MS instruments can be equipped with at leastthree types of soft ionization techniques, that is, ESI, APCI, andphotoionization. Up to now, articles on photoionization ofpesticides have been rarely published (Takino, Yamaguchi, &Nakahara, 2004). ESI and APCI are applied more often.Comparing the suitability of ESI versus APCI for the ionizationof many pesticides, electrospray was identified as more universaltechnique (Thurman, Ferrer, & Barcelo, 2001; Klein & Alder,2003; Jansson et al., 2004; Hernandez, Sancho, & Pozo, 2005).

C. Final Decision

Any of the instruments discussed above have special merits, butnone of them can detect the full range of all pesticides. However,if the selection of the most appropriate techniques is focused onthe enforcement of maximum residue levels, simultaneousidentification, and quantification of a very large number oftarget analytes will be more important than the detection,identification, and quantification of non-regulated (non-target)pesticides and/or metabolites. Under these conditions, EIionization and single quadrupole MS was identified as thepreferred GC detection system. If LC is used, most benefitsshould be obtained from tandem mass spectrometers operating inthe electrospray mode. Therefore, in the next section scope andsensitivity of GC-EI–MS will be compared to pesticide detectionby LC–ESI–tandem MS.

IV. COMPILATION OF EXISTING DATA

Characteristic ions of EI mass spectra, which are applied to thedetermination of pesticides by GC–MS, as well as typicaltransitions from precursor to product ions used for LC/tandemMS, are presented in Table 1.

Most of the cited articles contain information on thesensitivity of the instrument or method used. However, acomparison of such data is difficult. In some cases, sensitivity isbased on the signal-to-noise ratio of peaks in chromatograms ofstandards. In other studies, sensitivity is derived from the limit ofquantification (LOQ) of the complete analytical method. In thelatter case, the type of matrix and the concentration of the finalextracts have to be considered. Furthermore, sensitivity of instru-ments has improved significantly in the last years. Finally, severalparameters of GC–MS or LC–MS/MS measurement influence thesensitivity. In GC–MS such parameters are the dwell time, but alsothe type and length of column or temperature program. If LC–MS/MS is used, chromatography (e.g., type of solvent, buffer),

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ionization (e.g., ionization voltage, temperature, gas pressure), orparameters of ion measurement (e.g., dwell time, collision energy)can influence the sensitivity obtained. Therefore, data onsensitivity from different studies are often not comparable.

To compare the sensitivity of mass spectrometric determi-nation of pesticides avoiding these problems, the limits ofquantification presented in Table 1 were estimated by GC–MSand LC–MS/MS under identical conditions each.

A. GC–MS Data

Gas chromatography–mass spectrometry (GC–MS) has beenpracticed in analyzing pesticides for several decades andmost characteristic ions are available from pesticide analyticalmanuals, applications of instrument producers, or spectraldatabases supplied by producers of analytical standards. Inaddition, some excellent articles covering GC–MS analysis of abroad range of pesticides are published (Fillion, Sauve, &Selwyn, 2000; Wong et al., 2003; Chu, Hu, & Yao, 2005).Only for some pesticides, the characteristic ions in Table 1 areobtained from recent articles or studies conducted by the pesticideindustry.

For estimation of sensitivity, several mixed standards insolvent containing all pesticides were analyzed. A state-of-the-art GC–MS system (Agilent 6890N GC and 5975 inert MSD)using a pulsed pressure injection of 1 mL onto a HP-5 MS column(30 m� 0.25 mm� 0.25 mm), EI ionization, and a dwell timeof 40 msec were applied for each characteristic ion. The sameGC conditions were used for all injections. Obviously, a longerdwell time would result in better sensitivity, but—at the sametime—it would reduce the number of pesticides analyzed inone run.

Standard solutions containing 10,000, 1,000, 100, 10, and1 ng/mL were injected. If a pesticide was not detected at thehighest concentration in the SIM mode, no data were added toTable 1. In all other cases, characteristic ions are presented. TheLOQ was set to the lowest concentration, which gave a signal-to-noise ratio of �10 for the most intense peak of the analyte.

B. LC–MS/MS Data

Typical transitions from precursor to product ions are taken fromrecent publications, since analogous data collections do notexist for LC–MS/MS. SRM transitions from studies conductedwith triple quadrupole or quadrupole ion trap instrumentsare preferred. If such studies were not found, data onthose product ions are cited, which are produced in singlequadrupole instruments by increasing the potential betweenthe entrance capillary and the first skimmer (fragmentor or conevoltage). Often, transitions for a selected pesticide are publishedby more than two authors. In such cases, the citation in Table 1prefers the first or at least the earlier publications. However, notransitions were found in published studies for approximatelyone-third of the pesticides listed in Table 1. In such cases, typicaltransitions are taken from unpublished studies of pesticideproducers or from the world wide web (BfR, 2005).

The sensitivity of LC–MS/MS instruments was assessedusing a triple quadrupole mass spectrometer (API 4000,

Applied Biosystems) by injection of 20 mL analytical standardon a short reversed phase column (Phenomenex Aqua,50 mm� 2 mm� 5 mm), using a gradient of methanol/watercontaining 5 mmol/L ammonium formate. Approximately 100pesticide transitions were acquired simultaneously after ESIusing an identical dwell time of 20 msec for each SRM transition.

The batch used at the LC–MS/MS instrument includedstandard solutions with concentrations of 100, 10, 1, and 0.1 ng/mL. If a pesticide was not detected at the highest concentration inthe SRM mode, no data were added to Table 1. In all other cases,typical transitions are presented. The LOQ was set to the lowestconcentration, which gave a signal-to-noise ratio of �10 for themost intense peak of the analyte.

V. CONCLUSIONS FROM COMPILED DATA

A. Comparison of Scope of Both Techniques

The data in Table 1 demonstrate that more pesticides and theirmetabolites can be analyzed by LC and ESI than by GC–MS. It iswell known that sulfonyl or benzoyl ureas and many carbamatesor triazines can be better or exclusively detected by LC–MS/MStechniques. Furthermore, a wider scope of LC–MS/MS wasfound for most of the other chemical classes too, for example,the organophosphorus pesticides. Only 49 compounds out of500 exhibited no response, if LC–MS/MS in combinationwith positive and negative ESI was used. On the otherhand, 135 pesticides/metabolites could not be analyzed by GC/MS using EI ionization, most often because of incompatibilitywith evaporation of the intact molecule in the GC injector.

A more detailed overview presenting separate data forseveral chemical classes is given in Table 2. The data presentedin this table demonstrate clearly that several pesticides, whichare identified typically by an electron capture detector inGC measurements, do not show a sufficient LC–MS/MSresponse. This is well known for organochlorine compounds,but it is also valid for other pesticides like benfluralin,chlozolinate, dinobuton, etridiazole, flumethralin, nitrofen, orvinclozolin. The only exceptions are fenchlorphos, which isbetter detected by GC with flame photometric or nitrogen-phosphorus detection and biphenyl, which can be analyzed byGC–MS, only.

B. Comparison of Sensitivity

Both, GC–MS- and LC–MS-based methods, reveal a significantvariation of sensitivity, covering at least a range of 3–4 orders ofmagnitude, depending on the pesticide. However, a comparisonof the median of the limits of quantification clearly shows muchhigher sensitivity if determinations are based on LC and tandemMS. Most analytes may be quantified reliably by LC–MS/MS(at least in standard solutions) at concentrations between 0.1 and1 ng/mL. In contrast, the median of the limits of quantificationobserved by GC–MS is distinctly higher, that is, at 100 ng/mL.The distribution of LOQ data from Table 1 is summarizedseparately for both techniques in Figure 1. Nearly the samedistribution is found for organophosphorus pesticides, which are

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most often analyzed by GC methods up to now (Fig. 2). Ananalogous pattern is found for many other chemical classes ofpesticides.

Another approach that brings to the same conclusion ispresented in Figure 3. In this figure the percentage of thosepesticides that show a better response with GC–MS is comparedwith the percentage of compounds that are quantified with highersensitivity by LC–MS/MS. In addition to those 47 pesticides,which are not detected by LC–MS/MS at a level of 100 ng/mL,only two analytes (acrinathrin and procymidone) are analyzed

with better sensitivity by GC-MS. Finally, 19 pesticides(bromophos-ethyl, chlormephos, chlorobenzilate, chlorpyrifos-methyl, cyanofenphos, cyanophos, cycloate, cyhalofop-butyl,dichlofenthion, diphenylamine, esfenvalerate, fenitrothion, fen-valerate, lambda-cyhalothrin, methacrifos, parathion-methyl,phorate, prothiofos, tolclofos-methyl) are detected with an equalLOQ by GC–MS.

The better performance of LC–MS/MS is probablydetermined by several reasons. Among them the higher injectionvolume used in LC–MS/MS (20 mL vs. 1 mL) and the lower

TABLE 2. Pesticides, which are not covered by GC–MS or LC–MS/MS

*This calculation/list does not contain four organotin compounds, four quaternary ammonium salts,

glyphosate, and picloram, which require special LC conditions for ESI–MS/MS detection.

FIGURE 1. Distribution of limit of quantification (LOQ) data of all

pesticides/metabolites.

FIGURE 2. Distribution of LOQ data of all organophosphorus pesti-

cides.

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amount of fragmentation during ionization (ESI vs. EI) mayexplain some of these differences.

C. Conclusions and Perspectives forMulti-Residue Methods

Gas chromatography (GC) coupled to EI-MS and LC combinedwith tandem MS are the most important detection techniques inpesticide residue analysis today. The comparison of scope andsensitivity of both techniques presented above has illustrated thebetter performance of LC–MS/MS.

While establishing the measurements of hundreds of LOQs,another important advantage of LC–MS/MS became clear. Dueto the small peak width in GC, the cycle time in GC–MS methodsmust be 1 sec or shorter. Since all ions are recorded using a dwelltime of 40 msec, not more than 25 characteristic ions can berecorded in one time window. Assuming 10 time windows in oneGC run, 250 ions or 83 pesticides with 3 characteristic ions eachcan be analyzed in parallel theoretically. The peak width in LCmeasurements is usually higher, often allowing a typical cycletime of 2.5 sec. Based on the dwell time of 20 msec used forthe data in Table 1, approximately 125 SRM transitions canbe acquired simultaneously in one time window. Assuming5 time windows per LC run in that case, 625 SRM transitions areobtained with one injection. Since two SRM transitions are oftensufficient to quantify and confirm a result, up to 312 pesticidescan be analyzed theoretically in one run. In practice, thetheoretical numbers calculated above cannot be reached becauseusually more pesticides elute in the middle than in the beginningor end of the chromatograms. However, irrespective of thislimitation, the number of analytes covered in one LC–MS/MSrun is at least two or three times higher than the number ofpesticides measured in parallel by GC–MS in the SIM mode.

The comparison of both techniques would remain incom-plete, if the influence of matrix on the determination is not

considered. Matrix effects on the analyte transmission from theGC injector to the column (Hajslova & Zrostlikova, 2003) orinhibition of ESI (Bester et al., 2001; Stuber & Reemtsma, 2004)are well known phenomena. In both cases the use of matrixmatched standards can reduce the problem, but preparation ofsuch standards is laborious and appropriate sample materialswithout any residues are not generally available. Therefore, theuse of surface protectants is an interesting alternative (Anastas-siades, Mastovska, & Lehotay, 2003), which is applicable for GCmethods but not for LC–MS/MS. In several cases, the influenceof coeluting matrix peaks on the atmospheric pressure ionizationcan be reduced by the ECHO technique (Zrostlikova et al., 2002),but a general compensation of matrix effects is not obtained(Alder et al., 2004). Using LC–MS/MS, the simplest alternativeis the dilution of extracts. However, such dilution requires residueconcentrations distinctly above the LOQ. If no otherchoice exists, the method of standard addition will solve thisproblem of accurate quantification.

In addition to the effect on response, matrix componentsproduce several additional signals in chromatograms. Suchinterferences are not seldom if extracts of complex matrices (i.e.,herbs or tea) are analyzed by GC–MS. False positive identifica-tions of pesticides may be a consequence. Matrix interference issignificantly reduced if tandem MS is used. From that reason, LC–MS/MS methods do not require such an extensive cleanup andsophisticated chromatographic separation (Stout et al., 1998).Different molecules that share the same transition are more rarelyfound than molecules producing fragments of identical mass. As aconsequence, peak identification, integration, and data processingare much easier and faster in LC–MS/MS, and require less manualcorrections compared to GC–MS (Lehotay et al., 2005).

The discussion of many aspects of determination of pesticideresidues by GC–MS and LC–MS/MS clarified that neither MS incombination with GC nor the LC-based technique may solve allproblems of residue analysts. Both techniques and additionalones are needed today and will be needed in future. However, the

FIGURE 3. Comparison of GC–MS sensitivity versus LC–MS/MS sensitivity of individual pesticides

summarized for different pesticide classes.

RESIDUE ANALYSIS OF 500 HIGH PRIORITY PESTICIDES &

Mass Spectrometry Reviews DOI 10.1002/mas 859

benefits of LC–MS/MS in terms of wider scope, increasedsensitivity, and better selectivity are obvious. These character-istics, together with the ability to perform most determinationswithout derivatization, make LC–MS/MS the preferred techni-que currently available for the determination of pesticideresidues.

ACKNOWLEDGMENTS

We thank Volker Happel and Marilyn Menden for their supportneeded for the determination of limits of quantification. NatasaMarkovic, Birgit Mueller, and Annamaria Melcher providedimportant technical assistance throughout this work.

REFERENCES

Agilent Technologies. 1999. RTL Pesticide MS Library. Product No. G1049A.

URL available: http://www.chem.agilent.com/ecommerce/product/

product_catalog_3.aspx?groupid¼&sid¼none&catid¼&subcatid¼&pid¼388832.

Aguera A, Contreras M, Crespo J, Fernandez-Alba AR. 2002. Multiresidue

method for the analysis of multiclass pesticides in agricultural products

by gas chromatography-tandem mass spectrometry. Analyst 127:347–

354.

Aguera A, Lopez S, Fernandez-Alba AR, Contreras M, Crespo J, Piedra L.

2004. One-year routine application of a new method based on liquid

chromatography-tandem mass spectrometry to the analysis of 16

multiclass pesticides in vegetable samples. J Chromatogr A 1045:125–

135.

Alder L, Luderitz S, Lindtner K, Stan HJ. 2004. The ECHO technique—the

more effective way of data evaluation in liquid chromatography-tandem

mass spectrometry analysis. J Chromatogr A 1058:67–79.

Anastassiades M, Mastovska K, Lehotay SJ. 2003. Evaluation of analyte

protectants to improve gas chromatographic analysis of pesticides.

J Chromatogr A 1015:163–184.

Anastassiades M, Scherbaum E, Schwack W. 2000. Multiresidue method for

the determination of pre- and postharvest pesticides in citrus fruits—

Part 4: Determination of organotin pesticides. Deut Lebensm-Rundsch

96:466–477.

Anspach T. 2003. Enforcement method for the determination of BAS 518 H

and its metabolites BAS 518-2 and BAS 518-4 in/on materials of plant

origin—independent laboratory validation. BASF DocID 2003/

1001273 (March 21, 2003), BASF Aktiengesellschaft, BASF Agricul-

tural Center Limburgerhof, Germany.

Artigas F, Martinez E, Gelpi E. 1988. Organochlorine pesticides by negative-

ion chemical ionization—Brain-metabolites of Lindane. Biomed

Environ Mass Spectrom 16:279–284.

Asperger A, Efer J, Koal T, Engewald W. 2001. On the signal response of

various pesticides in electrospray and atmospheric pressure chemical

ionization depending on the flow-rate of eluent applied in liquid

chromatography-tandem mass spectrometry. J Chromatogr A 937:65–

72.

Ayano E, Kanazawa H, Ando M, Nishimura T. 2004. Determination and

quantitation of sulfonylurea and urea herbicides in water samples using

liquid chromatography with electrospray ionization mass spectrometric

detection. Anal Chim Acta 507:211–218.

Bacher R. 2002. Development and validation of an analytical method for the

determiantion of diflufenican in soil. Bayer CropScience Study No.

02F033 (August 30, 2002), Bayer Crop Science, Germany.

Baglio D, Kotzias D, Larsen BR. 1999. Atmospheric pressure ionisation

multiple mass spectrometric analysis of pesticides. J Chromatogr A

854:207–220.

Barnes KA, Fussell RJ, Startin JR, Mobbs HJ, James R, Reynolds SL. 1997.

Determination of the pesticide fenbutatin oxide in tomatoes, cucumbers

and bananas by high performance liquid chromatographic atmospheric

pressure chemical ionization-mass spectrometry. Rapid Commun Mass

Spectrom 11:159–164.

Benwell L, Burden AN. 1995. MON65500: The development and validation

of an analytical method for the determination of residues in wheat

grain and straw. Report No.: 64/53-1012 (November 23, 1995),

Monsanto Europe SA, Technical Center Europe, Louvain-La-Neuve,

Belgium.

Benz A, Mackenroth Ch. 2001. Validation of BASF method No. 472/0:

Determination of BAS 615 H and BH 615-3 in cereal forage, grain and

straw. Study Code 96355 (April 6, 2001), BASF Aktiengesellschaft,

BASF Agricultural Center Limburgerhof, Germany.

Bester K, Bordin G, Rodriguez A, Schimmel H, Pauwels J, Van Vyncht G.

2001. How to overcome matrix effects in the determination of pesticides

in fruit by HPLC-ESI-MS-MS. Fresenius J Anal Chem 371:550–555.

BfR. 2005. Parameters for the determination of pesticide residues. URL

available: http://www.bfr.bund.de/cd/5832.

Blasco C, Font G, Pico Y. 2004. Determination of dithiocarbamates and

metabolites in plants by liquid chromatography-mass spectrometry.

J Chromatogr A 1028:267–276.

Blasco C, Pico Y, Font G. 2002. Monitoring of five postharvest fungicides in

fruit and vegetables by matrix solid-phase dispersion and liquid

chromatography/mass spectrometry. J AOAC Int 85:704–711.

Blasco C, Font G, Manes J, Pico Y. 2003. Solid-phase microextraction liquid

chromatography/tandem mass spectrometry to determine postharvest

fungicides in fruits. Anal Chem 75:3606–3615.

Borba da Cunha AC, Lopez de Alda MJ, Barcelo D, Pizzolato TM, dos Santos

JH. 2004. Multianalyte determination of different classes of pesticides

(acidic, triazines, phenyl ureas, anilines, organophosphates, molinate

and propanil) by liquid chromatography-electrospray-tandem mass

spectrometry. Anal Bioanal Chem 378:940–954.

Bossi R, Vejrup KV, Mogensen BB, Asman WA. 2002. Analysis of polar

pesticides in rainwater in Denmark by liquid chromatography-tandem

mass spectrometry. J Chromatogr A 957:27–36.

Bourgade Ch, Chapius M-P, Diot R, Kieken J-L. 1999. Fenamidone

(RPA407213) and its metabolites (RPA405862, RPA408056 and

RPA717879): Analytical method for the determination of residues in

drinking water and surface water. Study No.: 98–218 (June 28, 1999),

Rhone-Poulenc Agro, Centre de Recherche de la Dargoire, Lyon, France.

Bourry R, Gasser A, Hertl P, Karapally J. 1991. A method for the

determination of residues of cyproconazole in various environmental

matrices. SDZ 401/930491, Dok. No. BS 2598/5407 (October 24,

1991), Sandoz Agro Ltd., Development Region Basle, Analytical

Chemistry and Environmental Sciences, Basle, Switzerland.

Briand O, Millet M, Bertrand F, Clement M, Seux R. 2002. Assessing the

transfer of pesticides to the atmosphere during and after application.

Development of a multiresidue method using adsorption on Tenax and

thermal desorption-GC/MS. Anal Bioanal Chem 374:848–857.

Bruns G, Tauber RaGR. 1999. Validation of the method of analysis for

Ethylenethiourea (ETU) in water by LC/MS/MS. Sponsor Study No.

ETU01ETL, ETL Reference No. 99RHC42.REP (July 14 1999),

EBDC/ETU Task Force: Rhohm & Haas Company, Elf Atochem North

America, Inc., Griffin L.L.C., BASF Cooporation.

Cabras P, Angioni A, Garau VL, Melis M, Pirisi FM, Cabitza F, Dedola F,

Navickiene S. 1998a. Determination of buprofezin, pyridaben, and

tebufenpyrad residues by gas chromatography mass-selective detection

in clementine citrus. J Agric Food Chem 46:4255–4259.

Cabras P, Angioni A, Garau VL, Pirisi FM, Brandolini V. 1998b. Gas chro-

matographic determination of azoxystrobin, fluazinam, kresoxim-methyl,

& ALDER ET AL.

860 Mass Spectrometry Reviews DOI 10.1002/mas

mepanipyrim, and tetraconazole in grapes, must, and wine. J AOAC Int

81:1185–1189.

Cairns T, Chiu KS, Navarro D, Siegmund E. 1993. Multiresidue pesticide

analysis by ion-trap mass-spectrometry. Rapid Commun Mass

Spectrom 7:971–988.

Cajka T, Hajslova J. 2004. Gas chromatography-high-resolution time-of-

flight mass spectrometry in pesticide residue analysis: Advantages and

limitations. J Chromatogr A 1058:251–261.

Castro R, Moyano E, Galceran MT. 2001. Determination of quaternary

ammonium pesticides by liquid chromatography-electrospray tandem

mass spectrometry. J Chromatogr A 914:111–121.

Chaler R, Vilanova R, Santiago-Silva M, Fernandez P, Grimalt JO. 1998.

Enhanced sensitivity in the analysis of trace organochlorine compounds

by negative-ion mass spectrometry with ammonia as reagent gas.

J Chromatogr A 823:73–79.

Chen AW. 2005. ELISA and liquid chromatography/mass spectrometry/

mass spectrometry methods for sulfentrazone and its acid meta-

bolite in groundwater samples. New Discov Agrochem 892:295–

303.

Chu XG, Hu XZ, Yao HY. 2005. Determination of 266 pesticide residues in

apple juice by matrix solid-phase dispersion and gas chromatography-

mass selective detection. J Chromatogr A 1063:201–210.

Class T. 2001. Analytical method for the determination of Pyraflufen-ethyl

(ET-751) and its acid metabolite E-1 in soil. Method AR 278-01, PTRL

Study No. P 469 G, Aventis CropScience Study No. 01–14 (September

14, 2001), Aventis CropScience, Frankfurt, Germany.

Crescenzi C, DiCorcia A, Guerriero E, Samperi R. 1997. Development of a

multiresidue method for analyzing pesticide traces in water based on

solid-phase extraction and electrospray liquid chromatography mass

spectrometry. Environ Sci Technol 31:479–488.

Dalluge J, Roose P, Brinkman UAT. 2002. Evaluation of a high-resolution

time-of-flight mass spectrometer for the gas chromatographic determi-

nation of selected environmental contaminants. J Chromatogr A 970:

213–223.

Dalluge J, van Stee LLP, Xu XB, Williams J, Beens J, Vreuls RJJ, Brinkman

UAT. 2002. Unravelling the composition of very complex samples by

comprehensive gas chromatography coupled to time-of-flight mass

spectrometry—Cigarette smoke. J Chromatogr A 974:169–184.

de Koning S, Lach G, Linkerhagner M, Loscher R, Horst TP, Brinkman UA.

2003. Trace-level determination of pesticides in food using difficult

matrix introduction-gas chromatography-time-of-flight mass spectro-

metry. J Chromatogr A 1008:247–252.

Di Corcia A, Nazzari M, Rao R, Samperi R, Sebastiani E. 2000. Simultaneous

determination of acidic and non-acidic pesticides in natural waters by

liquid chromatography-mass spectrometry. J Chromatogr A 878:87–98.

Draper WM. 2002. Near UV quantum yields for rotenone and piperonyl

butoxide. Analyst 127:1370–1374.

Ehrenstorfer GmbH. 2005. Library of Mass Spectra. Catalog No. B

01000000. URL available: http://www.analytical-standards.com.

Evans CS, Startin JR, Goodall DM, Keely BJ. 2001. Tandem mass

spectrometric analysis of quaternary ammonium pesticides. Rapid

Commun Mass Spectrom 15:699–707.

Fernandez M, Pico Y, Girotti S, Manes J. 2001a. Analysis of organopho-

sphorus pesticides in honeybee by liquid chromatography-atmospheric

pressure chemical ionization-mass spectrometry. J Agric Food Chem

49:3540–3547.

Fernandez M, Rodriguez R, Pico Y, Manes J. 2001b. Liquid chromatographic-

mass spectrometric determination of postharvest fungicides in citrus

fruits. J Chromatogr A 912:301–310.

Ferrer I, Garcia-Reyes JF, Mezcua M, Thurman EM, Fernandez-Alba AR.

2005. Multi-residue pesticide analysis in fruits and vegetables by liquid

chromatography-time-of-flight mass spectrometry. J Chromatogr A

1082:81–90.

Fillion J, Sauve F, Selwyn J. 2000. Multiresidue method for the determination

of residues of 251 pesticides in fruits and vegetables by gas

chromatography/mass spectrometry and liquid chromatography with

fluorescence detection. J AOAC Int 83:698–713.

Fischer R, Haenel R, Siebers J. 2003b. Residue analysis of new pesticides. 9

Indoxacarb, picolinafen. Nachrichtenbl Dtsch Pflanzenschutzd 55:29–38.

Fischer R, Franz H, Haenel R, Siebers J. 2003a. Residue analysis of new

pesticides. 10 Pyraclostrobin. Nachrichtenbl Dtsch Pflanzenschutzd

55:189–197.

Freitas LG, Gotz CW, Ruff M, Singer HP, Muller SR. 2004. Quantification of

the new triketone herbicides, sulcotrione and mesotrione, and other

important herbicides and metabolites, at the ng/l level in surface waters

using liquid chromatography-tandem mass spectrometry. J Chromatogr

A 1028:277–286.

Frenich AG, Garcia MDG, Arrebola FJ, Vidal JLM, Galera MM, Lopez T.

2000. Determination of parts per trillion levels of benzoylurea

pesticides in groundwater by high-performance liquid chromatogra-

phy-electrospray ionization mass spectrometry. Chromatographia 52:

569–574.

Fuchsbichler G. 2000. Independent Laboratory Validation of Analytical

Method AR 165-198 for the Determination of Pyraflufen-ethyl (ET-

751) in Cereal (Winter Wheat). Report No. HVA 22/00/Aventis

CropScience Study No. 00–149/C011460 (October 24, 2000),

Bayerische Hauptversuchsanstalt fur Landwirtschaft der TUM-Wei-

henstephan, Abteilung Ruckstandsanalytik, Freising, Germany.

Funk H, Mackenroth Ch. 2001. Validation of BASF method no. 445/0:

Determination of BAS 510 F in plant matrices. Study Code 41840

(February 19, 2001), BASF Aktiengesellschaft, BASF Agricultural

Center Limburgerhof, Germany.

Gamon M, Lleo C, Ten A, Mocholi F. 2001. Multiresidue determination of

pesticides in fruit and vegetables by gas chromatography/tandem mass

spectrometry. J AOAC Int 84:1209–1216.

Garcia-Reyes JF, Ferrer I, Thurman EM, Molina-Diaz A, Fernandez-Alba

AR. 2005. Searching for non-target chlorinated pesticides in food by

liquid chromatography/time-of-flight mass spectrometry. Rapid Com-

mun Mass Spectrom 19:2780–2788.

Ghini S, Fernandez M, Pico Y, Marin R, Fini F, Manes J, Girotti S. 2004.

Occurrence and distribution of pesticides in the province of Bologna,

Italy, using honeybees as bioindicators. Arch Environ Contam Toxicol

47:479–488.

Goncalves C, Alpendurada MF. 2004. Solid-phase micro-extraction-

gas chromatography-(tandem) mass spectrometry as a tool for

pesticide residue analysis in water samples at high sensitivity and

selectivity with confirmation capabilities. J Chromatogr A 1026:239–

250.

Goodenowe DB, Orescan DB, Babicki WA, Jr. 1999. Multianalyte method for

the simultaneous quantitation and confirmation of 21 sulfonylurea

Herbicides in soil using electrospray LC-triple-stage quadrupole mass

spectrometry. Report No AMR 4808–4897 (April 15, 1999), E.I. du

Pont de Nemours and Company, DuPont Agricultural Products, Global

Technology Division, USA.

Granby K, Andersen JH, Christensen HB. 2004. Analysis of pesticides in

fruit, vegetables and cereals using methanolic extraction and detection

by liquid chromatography-tandem mass spectrometry. Anal Chim Acta

520:165–176.

Granby K, Johannesen S, Vahl M. 2003. Analysis of glyphosate residues in

cereals using liquid chromatography-mass spectrometry (LC-MS/MS).

Food Addit Contam 20:692–698.

Guillet M, Jendrzejczak N, Chapuis Ch, Mauger L, Kieken J-L. 1999.

Fenamidone (RPA407213) and its metabolites (RPA408056 and

RPA717879): Analytical method for the determination of residues in

products of animal origin. Study No.: 98–150 (AR 178–98) (June 07,

1999), Rhone-Polenc AGRO, Centre de Recherche de la Dargoire,

Lyon, France.

RESIDUE ANALYSIS OF 500 HIGH PRIORITY PESTICIDES &

Mass Spectrometry Reviews DOI 10.1002/mas 861

Haenel R, Fischer R, Siebers J. 2002. Residue analysis of new pesticides. 8

Clethodim, dimethenamid-P, iprovalicarb, mesotrione, sulfosulfuron.

Nachrichtenbl Dtsch Pflanzenschutzd 54:217–225.

Haib J, Hofer I, Renaud JM. 2003. Analysis of multiple pesticide residues in

tobacco using pressurized liquid extraction, automated solid-phase

extraction clean-up and gas chromatography-tandem mass spectro-

metry. J Chromatogr A 1020:173–187.

Hajslova J, Zrostlikova J. 2003. Matrix effects in (ultra)trace analysis of

pesticide residues in food and biotic matrices. J Chromatogr A 1000:

181–197.

Hall GL, Engebretson J, Hengel MJ, Shibamoto T. 2004. Analysis of

methoxyfenozide residues in fruits, vegetables, and mint by liquid

chromatography-tandem mass spectrometry (LC-MS/MS). J Agric

Food Chem 52:672–676.

Hargreaves SL. 1999. Analytical method for the Determination of Residues of

Pirimicarb, Prosulfocarb, Picoxystrobin and Flutriafol in Water Technical

Letter 49045/01 and 46932/01 (December 09, 1999), Zeneca Agrochem-

icals, Jealott’s Hill Research Station, Bracknell, Berkshire, UK.

Hargreaves S. 2004. Residue analytical method for the determination of

residues of trinexapac-ethyl in soil. Standard operation procedure RAM

436/01, CGA 163935/0947 (June 21, 2004), Syngenta, Jealott’s Hill

International Research Center, Berkshire, UK.

Hengel MJ, Shibamoto T. 2002. Method development and fate determination

of pesticide-treated hops and their subsequent usage in the production of

beer. J Agric Food Chem 50:3412–3418.

Henriksen T, Svensmark B, Juhler RK. 2002. Analysis of Metribuzin and

transformation products in soil by pressurized liquid extraction and

liquid chromatographic-tandem mass spectrometry. J Chromatogr A

957:79–87.

Hernandez F, Sancho JV, Pozo OJ. 2005. Critical review of the application of

liquid chromatography/mass spectrometry to the determination of

pesticide residues in biological samples. Anal Bioanal Chem 382:934–

946.

Hernandez F, Sancho JV, Pozo O, Lara A, Pitarch E. 2001. Rapid direct

determination of pesticides and metabolites in environmental water

samples at sub-microg/l level by on-line solid-phase extraction-liquid

chromatography-electrospray tandem mass spectrometry. J Chroma-

togr A 939:1–11.

Hernandez F, Ibanez M, Sancho JV, Pozo OJ. 2004. Comparison of different

mass spectrometric techniques combined with liquid chromatography

for confirmation of pesticides in environmental water based on the use

of identification points. Anal Chem 76:4349–4357.

Hernando MD, Aguera A, Fernandez-Alba AR, Piedra L, Contreras M. 2001.

Gas chromatographic determination of pesticides in vegetable samples

by sequential positive and negative chemical ionization and tandem

mass spectrometric fragmentation using an ion trap analyser. Analyst

126:46–51.

Hetherton CL, Sykes MD, Fussell RJ, Goodall DM. 2004. A multi-residue

screening method for the determination of 73 pesticides and metabolites

in fruit and vegetables using high-performance liquid chromatography/

tandem mass spectrometry. Rapid Commun Mass Spectrom 18:2443–

2450.

Hogenboom AC, Niessen WM, Little D, Brinkman UA. 1999. Accurate mass

determinations for the confirmation and identification of organic

microcontaminants in surface water using on-line solid-phase extrac-

tion liquid chromatography electrospray orthogonal-acceleration time-

of-flight mass spectrometry. Rapid Commun Mass Spectrom 13:125–

133.

Hui JY, Aizawa T, Magara Y. 1999. Analysis of pesticides in water with liquid

chormatography/atmospheric pressure chemical ionization mass spec-

trometry. Water Res 33:417–425.

Ingelse BA, van Dam RCJ, Vreeken RJ, Mol HGJ, Steijger OM. 2001.

Determination of polar organophosphorus pesticides in aqueous

samples by direct injection using liquid chromatography-tandem mass

spectrometry. J Chromatogr A 918:67–78.

Jansson C, Pihlstrom T, Osterdahl BG, Markides KE. 2004. A new multi-

residue method for analysis of pesticide residues in fruit and vegetables

using liquid chromatography with tandem mass spectrometric detec-

tion. J Chromatogr A 1023:93–104.

Jeannot R, Sabik H, Sauvard E, Genin E. 2000. Application of liquid

chromatography with mass spectrometry combined with photodiode

array detection and tandem mass spectrometry for monitoring

pesticides in surface waters. J Chromatogr A 879:51–71.

Juan-Garcia A, Font G, Pico Y. 2005. Quantitative analysis of six pesticides in

fruits by capillary electrophoresis-electrospray-mass spectrometry.

Electrophoresis 26:1550–1561.

Juan-Garcia A, Manes J, Font G, Pico Y. 2004. Evaluation of solid-phase

extraction and stir-bar sorptive extraction for the determination of

fungicide residues at low-microg kg(-1) levels in grapes by liquid

chromatography-mass spectrometry. J Chromatogr A 1050:119–127.

Juhler RK, Vahl M. 1999. Residues of chlormequat and mepiquat in grain—

Results from the Danish National Pesticide Survey. J AOAC Int 82:

331–336.

Kaune A. 2001. Validation of the analytical method EM F02/01-0

for the determination of AE F1079892 and its metabolites AE

F113225, AE F109453 and AE F094270 in water and storage stability

in water. C013908! 01F004 (June 29, 2001), Aventis CropSciences

GmbH, Residues and Human Exposure, Frankfurt/Main, Germany.

Kerl W. 2002. Validation of the analytical method 494/0: Method for the

determination of BAS 119 H in plant matrices. Study code 121483

(August 29, 2002), BASF Aktiengesellschaft, BASF Agricultural

Center Limburgerhof, Germany.

Klein J, Alder L. 2003. Applicability of gradient liquid chromatography with

tandem mass spectrometry to the simultaneous screening for about 100

pesticides in crops. J AOAC Int 86:1015–1037.

Knoch E. 2002. Method validation—determination of Flumioxazin in water.

Institut Fresenius Project Identification IF-02/00015115 (September 04,

2002); Sumitomo Chemical Agro Europe S.A., St Diedier au Mont

d’Or, France.

Koal T, Asperger A, Efer J, Engewald W. 2003. Simultaneous determination

of a wide spectrum of pesticides in water by means of fast on-line SPE-

HPLC-MS-MS—a novel approach. Chromatographia 57:93–101.

Lagana A, Fago G, Marino A, Mosso M. 1998. Soil column extraction

followed by liquid chromatography and electrospray ionization mass

spectrometry for the efficient determination of aryloxyphenoxypropio-

nic herbicides in soil samples at ng g(-1) levels. Anal Chim Acta 375:

107–116.

Lagana A, Bacaloni A, De Leva I, Faberi A, Fago G, Marino A. 2002.

Occurrence and determination of herbicides and their major transfor-

mation products in environmental waters. Anal Chim Acta 462:187–

198.

Laporte F. 2001. Determination of residues of triticonazole in air: Use of GC-

MS as confirmatory technique. Code AE C632720/ C014405 (July 13,

2001), Aventis CropSciences GmbH, Residues and Human Exposure,

Frankfurt/Main, Germany.

Leandro CC, Fussell RJ, Keely BJ. 2005. Determination of priority pesticides

in baby foods by gas chromatography tandem quadrupole mass

spectrometry. J Chromatogr A 1085:207–212.

Lehotay SJ, de Kok A, Hiemstra M, van Bodegraven P. 2005. Validation

of a fast and easy method for the determination of residues from

229 pesticides in fruits and vegetables using gas and liquid

chromatography and mass spectrometric detection. J AOAC Int 88:

595–614.

Maizels M, Budde WL. 2001. Exact mass measurements for confirmation of

pesticides and herbicides determined by liquid chromatography/time-

of-flight mass spectrometry. Anal Chem 73:5436–5440.

Marek LJ, Koskinen WC, Bresnahan GA. 2000. LC/MS analysis of

cyclohexanedione oxime herbicides in water. J Agric Food Chem

48:2797–2801.

& ALDER ET AL.

862 Mass Spectrometry Reviews DOI 10.1002/mas

Martinez Vidal JL, Arrebola FJ, Mateu-Sanchez M. 2002. Application of gas

chromatography-tandem mass spectrometry to the analysis of pesti-

cides in fruits and vegetables. J Chromatogr A 959:203–213.

Memmesheimer H. 1999. AC 900001 (CL 900001): Validation of method

FAMS 109-01 for the determination of AC 900001 and CL 153815

residues in animal tissues (milk, meat, eggs and fat). Study No.

DER134, Repoert No. CFS 1999-010 (January 28, 1999), Cyanamid

Forschung GmbH (CFS), Schwabenheim, Germany.

Mol HGJ, van Dam RCJ, Steijger OM. 2003. Determination of polar

organophosphorus pesticides in vegetables and fruits using liquid

chromatography with tandem mass spectrometry: Selection of extrac-

tion solvent. J Chromatogr A 1015:119–127.

Nauen R, Ebbinghaus-Kintscher U, Salgado VL, Kaussmann M. 2003.

Thiamethoxam is a neonicotinoid precursor converted to clothianidin in

insects and plants. Pest Biochem Physiol 76:55–69.

Navalon A, Prieto A, Araujo L, Vilchez JL. 2002. Determination of

pyrimethanil and kresoxim-methyl in green groceries by headspace

solid-phase microextraction and gas chromatography-mass spectro-

metry. J Chromatogr A 975:355–360.

Nett MT, Lipton CR. 1994. Tefluthrin: Validation of an analytical method for

the determination of Tefluthrin residues in soil/water slurry (WCR-92-

017) (WINO 2419). Report No. RR 92-013B (July 21, 1994), Zeneca Ag

Products, Western Research Center.

Neuss B, Losse K. 1999. Analytical method and validation for the

determination of AE F122006 and its metabolite AE C637375 in rice

grain. C004156 (June 10, 1999), Hoechst Schering AgrEvo GmbH,

Entwicklung, Ruckstande und Verbrauchersicherheit, Frankfurt/Main,

Germany.

Neuss B, Schuld G. 1999. Analytical method and validation for the

determination of residues of AE F122006 and its metabolites in rice

using LC-MS/MS. Method No. DGM F02/98-0, Laboratory identifica-

tion code CR98/020 (March 23, 1999), AgrEvo GmbH, Rueckstaende

und Verbrauchersicherheit, Frankfurt, Germany.

NIST/EPA/NIH. 2005. Mass Spectral Database, 2005. National Insitute of

Standards and Technology. Gaithersburg, MD. URL available: http://

www.nist.gov/srd/nist1.htm.

Nuesslein F. 1999. Residue analytical method 00552 for the determination of

TI 435 in plant materials by LC-MS/MS. Report MR-036/99 (August

19, 1999), Bayer AG, PF-E/MR, Leverkusen, Germany.

Nunez O, Moyano E, Galceran MT. 2004. Time-of-flight high resolution

versus triple quadrupole tandem mass spectrometry for the analysis of

quaternary ammonium herbicides in drinking water. Anal Chim Acta

525:183–190.

Ortelli D, Edder P, Corvi C. 2004. Multiresidue analysis of 74 pesticides in

fruits and vegetables by liquid chromatography-electrospray-tandem

mass spectrometry. Anal Chim Acta 520:33–45.

Patel K, Fussell RJ, Goodall DM, Keely BJ. 2004. Evaluation of largevolume-

difficult matrix introduction-gas chromatography-time of flight-mass

spectrometry (LV-DMI-GC-TOF-MS) for the determination of pesti-

cides in fruit-based baby foods. Food Add Contam 21:658–669.

Pelz S, Steinhauer S. 2001. BAS 560F (AC 375839): Validation of DFG

method S 19 for the determination of residues of BAS 560F in milk,

meat, and eggs. Final report BAS-0103V, DocID 2001/7000486

(November 13, 2001), BASF Agro Research, Princeton, NJ, USA.

Pfleger K, Maurer HH, Weber A. 2000. Mass spectral and gc data of drugs,

pollutants, pesticides and metabolites, 2nd edition. Weinheim: Wiley-

VCH. Parts I–IV.

Pico Y, Blasco C, Font G. 2004. Environmental and food applications of LC-

tandem mass spectrometry in pesticide-residue analysis: An overview.

Mass Spectrom Rev 23:45–85.

Pigeon IRO. 1999. Determination of residues of fosthiazate in potatoes after

treatment with ASCE 3829. Study No. 11250 (December 08, 1999),

Personnalite Juridique du Centre de Recherches Agronomiques de

Gembloux, Department de Phytopharmacie, Gembloux, Belgique.

Pointurier R. 2002. Determination of Dimethachlor (CGA17020), CGA

50266 and CGA 354742 in water by LC/MS. Residue method AGR/

MOA/DMC.6 (13.05.2002), Syngenta Crop Protection AG, Basel,

Switzerland.

Pous X, Ruiz MJ, Pico Y, Font G. 2001. Determination of imidacloprid,

metalaxyl, myclobutanil, propham, and thiabendazole in fruits and

vegetables by liquid chromatography-atmospheric pressure chemical

ionization-mass spectrometry. Fresenius J Anal Chem 371:182–189.

Ramesh A, Ravi PE. 2004. Negative ion chemical ionization-gas chromato-

graphic-mass spectrometric determination of residues of different

pyrethroid insecticides in whole blood and serum. J Anal Toxicol 28:

660–666.

Reichert N. 2003. Independent laboratory validation of the analytical method

for the determination of propaquizafop and propaquizafop-acid in

wheat (grain) and tomato (1st Amendment). Institut Fresenius project

no. IF-03/00061233 (September 26, 2003), Makhteshim-Agan

Deutschland GmbH, Germany.

Rial OR, Yague RC, Cancho GB, Simal GJ. 2002. Solid-phase microextrac-

tion-gas chromatographic-mass spectrometric method for the determi-

nation of the fungicides cyprodinil and fludioxonil in white wines.

J Chromatogr A 942:41–52.

Rippington D, Dick JP. 1990. ICI agrochemicals residue analytical method

No. 183: The determination of residues of pirimicarb and its desmethyl

metabolie in soil (October 17, 1990), ICI Agrochemicals, Jealott’s Hill

Research Station, Bracknell, Berkshire, UK.

Robinson NJ, Patel A. 1999. Residue analytical method for the analysis of

ZA1963 in cereal crops. Standard operation procedure RAM 288/01

(September 9, 1999), Zeneca Agrochemicals, Jealott’s Hill Research

Station, Berkshire, UK.

Rodriguez R, Manes J, Pico Y. 2003. Off-line solid-phase microextraction and

capillary electrophoresis mass spectrometry to determine acidic

pesticides in fruits. Anal Chem 75:452–459.

Rodriguez R, Pico Y, Font G, Manes J. 2002. Analysis of thiabendazole and

procymidone in fruits and vegetables by capillary electrophoresis-

electrospray mass spectrometry. J Chromatogr A 949:359–366.

Russo MV, Campanella L, Avino P. 2002. Determination of organopho-

sphorus pesticide residues in human tissues by capillary gas chromato-

graphy-negative chemical ionization mass spectrometry analysis.

J Chromatogr B Anal Technol Biomed Life Sci 780:431–441.

Rzepka S. 2004. Validation of the DFG method S 19 (extended and revised

version) for the determination of residues of flumioxazin in specimens

of cereals and other dry crops (wheat grain and straw). SUM-0350V!

G03-0129 (February 10, 2004), Sumitomo Chemical Agro Europe S.A.

(SCAE), St. Didier-auMont-d’ Or, France.

Saha M. 1997. Validation of BASF method no. D9606: Analytical method

validation for the determination of residues of BAS 620 H and its

metabolites (DP-6 and GP) in soil using LC-MS/MS. Study No. 96084

(March 14, 1997), BASF Cooperation, Agrucultural Products Group,

Research Triangle Park, USA.

Sancho JV, Pozo OJ, Hernandez F. 2004. Liquid chromatography and tandem

mass spectrometry: A powerful approach for the sensitive and rapid

multiclass determination of pesticides and transformation products in

water. Analyst 129:38–44.

Sannino A, Bolzoni L, Bandini M. 2004. Application of liquid chromato-

graphy with electrospray tandem mass spectrometry to the determina-

tion of a new generation of pesticides in processed fruits and vegetables.

J Chromatogr A 1036:161–169.

Schoning R, Seym M. 1998. Residue analytical method for the determination

of RH 2485 residues in/on plant material by HPLC with electrospray

MS/MS-detection. Method 00470, Study no. P 61260510 (September

16, 1998), Bayer AG, PF-E/MR, Leverkusen, Germany.

Schneider V. 2001. Determination of residue od UR 50601 (Beflubutamid)

in soil dissipation study with Herbaflex in Germany. Report No. PR00/

018 (January 19, 2001), UBE Industries Ltd., Shibaura Minato-Ku,

RESIDUE ANALYSIS OF 500 HIGH PRIORITY PESTICIDES &

Mass Spectrometry Reviews DOI 10.1002/mas 863

Tokyo, Japan und Stahler Agrochemie GmbH & Co. KG, Stade,

Germany.

Serodio P, Nogueira JM. 2005. Development of a stir-bar-sorptive extraction-

liquid desorption-large-volume injection capillary gas chromato-

graphic-mass spectrometric method for pyrethroid pesticides in water

samples 5. Anal Bioanal Chem 382:1141–1151.

Siebers J, Fischer R, Haenel R. 2000. Residue analysis of new pesticides. 6.

Azadirachtin (neem), carfentrazone, fenhexamid, flupyrsulfuron, iso-

xaflutol. Nachrichtenbl Dtsch Pflanzenschutzd 52:73–81.

Siebers J, Fischer R, Haenel R. 2001. Residue analysis of new pesticides.

7. Cinidon, famoxadone, florasulam, iodosulfuron, metconazol.

Nachrichtenbl Dtsch Pflanzenschutzd 53:1–10.

Smalley R. 2001. Method validation of RLA 12618.00 ‘‘LC-MS determina-

tion of CL 375839 and CL 377160 residues in soil’’. Report No. 4603,

BASF DocID 2001/7000247 (July 11, 2001), BASF Agro Research,

BASF plc., Hampshire, UK.

Smith K, Clouser-Roche A. 2001. Determination of BAS 635 H and

Metabolites BH 635-2, BH 635-3, BH 635-4 and BH 635-5 in soil by

LC/MS/MS. Method No. D9907, BASF Registration document no.

1999/5128 (January 24, 2001), BASF Corperation, Agricultural

Products Group, Research Triangle Park, USA.

Soler C, Manes J, Pico Y. 2004. Liquid chromatography-electrospray

quadrupole ion-trap mass spectrometry of nine pesticides in fruits.

J Chromatogr A 1048:41–49.

Soler C, Manes J, Pico Y. 2005. Comparison of liquid chromatography using

triple quadrupole and quadrupole ion trap mass analyzers to determine

pesticide residues in oranges. J Chromatogr A 1067:115–125.

Sommer H. 2002. Enforcement method no. 00758 for the determination of

residues of metosulam in soil by HPLC-MS/MS. Laboratory Project ID

P681020013 (July 18, 2002), Bayer AG, Business Group Crop

Protection, Leverkusen, Germany.

Sommer H. 2003. Enforcement method for the determination of Fuberidazole

in drinking and surface water by HPLC-MS/MS. Bayer CropScience

Report MR-525/01 (February 17, 2003), Bayer CropScience AG,

Development, Residues, Operator and Consumer Safety, Monheim,

Germany.

Souvignet I. 1999. Triticonazole: Validation of analytical method to

determine residues of triticonazole and its metabolite (RPA406341) in

soil. Covance Study No. 198/120, Sponsor Reference No. 98–180

(January 1999), Rhone-Poulenc Agro, Centre de Recherche de La

Dargoire, Lyon, France.

Stajnbaher D, Zupancic-Kralj L. 2003. Multiresidue method for determina-

tion of 90 pesticides in fresh fruits and vegetables using solid-phase

extraction and gas chromatography-mass spectrometry. J Chromatogr A

1015:185–198.

Stan HJ. 2000. Pesticide residue analysis in foodstuffs applying capillary gas

chromatography with mass spectrometric detection. State-of-the-art use

of modified DFG-multimethod S19 and automated data evaluation.

J Chromatogr A 892:347–377.

Stolker AAM, Niesing W, Hogendoorn EA, Rambali AB, Vleeming W. 2003.

Determination of nicotine and cotinine in rat plasma by liquid

chromatography-tandem mass spectrometry. J Chromatogr A 1020:

35–43.

Stout SJ, daCunha AR, Picard GL, Safarpour MM. 1998. Simplification of

analytical methods in pesticide residue analysis by liquid chromato-

graphy electrospray ionization mass spectrometry and tandem mass

spectrometry. J AOAC Int 81:685–690.

Stuber M, Reemtsma T. 2004. Evaluation of three calibration methods to

compensate matrix effects in environmental analysis with LC-ESI-MS.

Anal Bioanal Chem 378:910–916.

Sundaram KMS, Nott R, Lewin EE. 1994. Comparative-Study of the

determination of Tebufenozide in formulated products by gas-

chromatographic and liquid-chromatographic methods. J Chromatogr

A 687:323–332.

Takino M, Yamaguchi K, Nakahara T. 2004. Determination of carbamate

pesticide residues in vegetables and fruits by liquid chromatography-

atmospheric pressure photoionization-mass spectrometry and atmo-

spheric pressure chemical ionization-mass spectrometry. J Agric Food

Chem 52:727–735.

Tate S. 2003. Validation of methodology for the determination of residues of

quizalofop-p-ethyl and quizalofop-p in drinking and ground water.

Project Identity NAS 559/033492 (September 30, 2003), Nissan

Chemical Industries, Ltd., Kowa Hitotsubashi Building, Tokyo, Japan.

Taylor MJ, Hunter K, Hunter KB, Lindsay D, Le Bouhellec S. 2002. Multi-

residue method for rapid screening and confirmation of pesticides in

crude extracts of fruits and vegetables using isocratic liquid chromato-

graphy with electrospray tandem mass spectrometry. J Chromatogr A

982:225–236.

Thier HP, Zeumer H. 1992. Manual of pesticide residue analysis, Vol. II.

Weinheim: Wiley VCH. pp 26–28.

Thurman EM, Ferrer I, Barcelo D. 2001. Choosing between atmospheric

pressure chemical ionization and electrospray ionization interfaces for

the HPLC/MS analysis of pesticides. Anal Chem 73:5441–5449.

Thurman EM, Ferrer I, Fernandez-Alba AR. 2005. Matching unknown

empirical formulas to chemical structure using LC/MS TOF accurate

mass and database searching: Example of unknown pesticides on

tomato skins. J Chromatogr A 1067:127–134.

Tomlin C.D.S. 2003. The pesticide manual—A world compendium, 13th

edition. Hampshire: British Crop Protection Council (BCPC).

Vahl M, Graven A, Juhler RK. 1998. Analysis of Chlormequat residues in

grain using liquid chromatography mass spectrometry (LC-MS/MS).

Fresenius J Anal Chem 361:817–820.

Valenzuela AI, Pico Y, Font G. 2000. Liquid chromatography/atmospheric

pressure chemical ionization-mass spectrometric analysis of benzoy-

lurea insecticides in citrus fruits. Rapid Commun Mass Spectrom

14:572–577.

van Zoonen P. 1998. Analytical methods for residues of psticides in

foodstuffs, 6th edition. Part I. Annex B. The Hague: General

Inspectorate for Health Protection. pp 1–8.

Vidal JLM, Frenich AG, Lopez TL, Salvador IM, el Hassani LH, Benajiba

MH. 2005. Selection of a representative matrix for calibration in

multianalyte determination of pesticides in vegetables by liquid

chromatography-electrospray tandem mass spectrometry. Chromato-

graphia 61:127–131.

Wais A. 2001. Validation of the residue analytical method for SL-160

(Flazasulfuron) in soil. RCC Study No. 802124 (October 17, 2001),

Ishihara Sangyo Kaisha. Ltd., Chiyoda-ku, Tokyo 102-0071, Japan.

Wang J, Cheung W, Grant D. 2005. Determination of pesticides in apple-

based infant foods using liquid chromatography electrospray ionization

tandem mass spectrometry. J Agric Food Chem 53:528–537.

Wang IH, Moorman R, Burleson J. 2003. Isocratic reversed-phase liquid

chromatographic method for the simultaneous determination of (S)-

methoprene, MGK264, piperonyl butoxide, sumithrin and permethrin

in pesticide formulation. J Chromatogr A 983:145–152.

Weber H, Pelz S. 2002. Enforcement method 00086/M040 for the

determination of the residues of Trifloxystrobin in cucumber (fruit),

citrus (fruit), wheat (grain), almond (seed), hop and leek. Report 00086/

M040 (February 26, 2002), Bayer AG, Landwirtschaftszentrum

Monheim, Leverkusen, Germany.

Weeren RD, Pelz S. 2001. Validation of dfg method s 19 (extended revision)

for the deternination of hexythiazox in plant materials (cucumber,

orange, corn, rapeseed and dried hops), 2001/1000931/BAS-0003V/

G00-0028 (January 25, 2001), BASF Aktiengesellschaft, BASF

Agricultural Center Limburgerhof, Germany.

Wong JW, Webster MG, Halverson CA, Hengel MJ, Ngim KK, Ebeler

SE. 2003. Multiresidue pesticide analysis in wines by solid-phase

extraction and capillary gas chromatography-mass spectrometric

& ALDER ET AL.

864 Mass Spectrometry Reviews DOI 10.1002/mas

detection with selective ion monitoring. J Agric Food Chem 51:1148 –

1161.

Yokley RA, Mayer LC, Huang SB, Vargo JD. 2002. Analytical method

for the determination of metolachlor, acetochlor, alachlor, dimethenamid,

and their corresponding ethanesulfonic and oxanillic acid degradates in

water using SPE and LC/ESI-MS/MS. Anal Chem 74: 3754–3759.

Zang XJ, Fukuda EK, Rosen JD. 1998. Multiresidue analytical procedure for

insecticides used by organic farmers. J Agric Food Chem 46:2206–

2210.

Zangmeister W. 1999. Validation of analytical method 455: Determination of

BAS 500 F, BF 500–11, BF 500–12, BF 500–13, BF 500–14 and BF

500–15 residues in water (tap water and surface water). Study No.

35888 (December 17, 1999), BASF Aktiengesellschaft, BASF Agri-

cultural Center Limburgerhof, Germany.

Zangmeister W. 2000. Validation of analytical method 460, determination

of BAS 510 F (Reg.no. 300355) in air by GC-MS. Study Code

41886, BASF DocID 2000/1014992 (October 19, 2000), BASF

Aktiengesellschaft, BASF Agricultural Center Limburgerhof, Germany.

Zimmer D. 2004. Enforcement method 00814/M001 for the determination

of residues of Mefenpyr-diethyl (AE F107892) and its metabolite

AE F094270 in/on plant material by HPLC-MS/MS. Report No. MR-

031/04 (August 25, 2004), Bayer CropScience AG, Monheim,

Germany.

Zrostlikova J, Hajslova J, Poustka J, Begany P. 2002. Alternative calibration

approaches to compensate the effect of co-extracted matrix components

in liquid chromatography-electrospray ionisation tandem mass spectro-

metry analysis of pesticide residues in plant materials. J Chromatogr A

973:13–26.

Zrostlikova J, Hajslova J, Kovalczuk T, Stepan R, Poustka J. 2003.

Determination of seventeen polar/thermolabile pesticides in apples

and apricots by liquid chromatography/mass spectrometry. J AOAC Int

86:612–622.

Zywitz D, Anastassiades M, Scherbaum E. 2003. Simultaneous determina-

tion of neonicotinoid insecticides in fruits and vegetables by LC-MS

and LC-MS-MS–Methodology and residue data. Deut Lebensm-

Rundsch 99:188–196.

Lutz Alder studied chemistry in Berlin/Germany with a focus on organic and analytical

chemistry. After his Ph.D. in 1978, he managed the mass spectrometry laboratory at

Humboldt University for several years. He has been employed by the Federal Health

Office, which is now the Federal Institute for Risk Assessment (BfR) since 1991. Most of

his research has been concerned with residue analytical methods and its standardization

for official use. He has published 50 scientific journal articles and book chapters.

Kerstin Greulich studied chemistry at Dresden Technical University focusing on

environmental chemistry. She received her Ph.D. at Humboldt University in 2004. At

present she is employed at the Federal Institute for Risk Assessment (BfR). Her research

interests involve residue analytical methods, environmental analysis, ecotoxicology, and

herpetology. She has published 12 scientific journal articles and book chapters.

Baerbel Vieth studied chemistry at the Humboldt University in Berlin. After finishing the

Ph.D. in 1981, her research has been focused on the development and application of HPLC

methods in trace analysis of drugs, enzyme activities, and of pesticides. In 1991, she joined

the former Federal Health Office of Germany, which is now the Federal Institute for Risk

Assessment (BfR). Besides residue analytical methods for pesticides, she has been

responsible for evaluation of residues in human milk with special focus on POPs. She has

published about 30 articles in scientific journals.

At present, Lutz Alder, Kerstin Greulich, and Baerbel Vieth are responsible for the

evaluation of residue analytical methods provided for registration of new pesticides in

Germany and contribute to authorization of plant protection products in Europe.

Guenther Kempe studied food chemistry and analytical chemistry in Dresden/Germany.

He started his career in the Hygiene Institute Chemnitz, which became the State Institute

for Food and Health Protection of Saxony/Germany in 1991. Most of his research has been

concerned with pesticide residue analysis in food. Today he is the head of the residue

laboratory of the State Institute and chairmen of the Working Group ’Pesticides’ of the

Gesellschaft Deutscher Chemiker (Chemical Society of Germany). His publication list

contains 20 scientific articles and book chapters.

RESIDUE ANALYSIS OF 500 HIGH PRIORITY PESTICIDES &

Mass Spectrometry Reviews DOI 10.1002/mas 865