©2015 Waters Corporation 1

©2015 Waters Corporation 2

Waters Corporation

Global leader with complementary analytical technologies

– Liquid chromatography, mass spectrometry

– Rheometry and microcalorimetry

Headquartered in Milford, MA

Year founded: 1958

About 6.000 employees

– 2.500-strong sales/service

James Waters Founder

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Waters Mission Statement

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Breakthrough Technologies

Since 1958 …………

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1963

First liquid separations System

ALC-100

1973

High-performance liquid chromatography

M6000 HPLC Pump

1978

Solid phase Extraction

Sep-Pak®

Cartridges

1988

PC-based Chromatography software

Maxima Software

1996 Time-of-flight MS

Q-TofTM Mass Spectrometer

2004

First UPLC® System

ACQUITY UPLC® System

2006

High-Definition MS

SYNAPT HDMSTM

System

2008/2009

XEVOTM TQ MS XEVO QTof MS

Breakthrough Technology

2007

Acquity UPLC H Class

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2011

XEVOTM TQD MS Synapt G2-S MS/HDMS UPLC Iclass UNIFY software

2010

XEVOTM TQ-S MS

2014 UPC ² Synapt G2-SI MS / HDMS QDa MS detector APC System

2012

XEVOTM G2-S Tof / QTof MS Nugenesis 8

Breakthrough Technology

2015 Vion IMS ToF Xevo TQ-S micro Oasis Prime

©2015 Waters Corporation 7

Global Manufacturing

• HPLC & UPLC Instruments & Accessories

• Machining Center produces 2.4M parts annually

Milford, Massachusetts, USA

• Particle Synthesis

• Column Packing

Taunton, Massachusetts, USA

• ToF & Sector based MS Instruments & Accessories

Manchester, UK

• Quadrupole MS Instruments & Accessories • Sample Prep & Column Packing • S/W Replication

Wexford, Ireland

• OEM Partners

• EMS Partners

Global Partners

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Glo

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tion

Cen

ters

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Manufactures under cGMP, ISO 9001 and ISO 13485 GL Registered with FDA as a medical device manufacturer

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Waters Revenue Distribution

North America 29%

Europe 29%

Latin America 8%

Asia Pacific 34%

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Core Competencies: A Total Systems Solution Approach

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Waters’ solution

in clinical laboratory

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Systems Solution for clinical laboratory

Liquid Chromatography Systems: • Alliance HPLC HPLC with quaternary pump • Acquity UPLC core UPLC with binary pump with an high pressure gradient mixing solution (CE-IVD) • Acquity UPLC H-Class UPLC with a quaternary pump, versatile • Acquity UPLC I-Class UPLC with binary pump an high pressure gradient mixing solution, with dead volume (<100 µL) and band spread (≈ 6 µL) very low (CE-IVD).

Mass Spectrometry Systems (Triple Quad): • TQD (CE-IVD) • Xevo TQD (CE-IVD) • Xevo TQ-S micro (CE-IVD) • Xevo TQ-S (CE-IVD)

©2015 Waters Corporation 13

CE-IVD Mark means: Controlled production with technical and electrical specifications suitable for the clinical market Analytical Performances of the instruments certified with documented tests Application notes and technical brief produced by Waters are controlled by external company before the final release Higher level of quality control in production Protocols of investigation of the different problems verified in the customers’ laboratories (AUDIT) Technical Service with technicians learned foth the GLP for the clinical laboratories

Why the CE-IVD mark is important?

©2015 Waters Corporation 14

Ideal Waters’ Clinical Solutions

Data receiving from LIS

Automation of the sample prep

Analysis in

LC-MS/MS

Results exported to

LIS

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Data receiving from LIS

Bi-directional interface with the most common LIS thanks to our HL-7 SW

Automation of the

sample prep Collaboration with Tecan and Hamilton Collaboration with Siemens and Abbott

Analysis in LC-MS/MS

TQD Xevo TQD Xevo TQ-S micro

Results exported

to LIS

Bi-directional interface with the most common LIS thanks to our HL-7 SW

©2015 Waters Corporation 16

Analysis in

LC-MS/MS

TDM Therapeutic Drug Monitoring Immunosuppressants Mycophenolic acid Antiretroviral Neuroleptics ed Antidepressants Antiepileptics Antibiotics Anticoagulants Antifungals Antitumorals

TQD

Clinical Biochemistry Steroids (not all) 25-OH-vitamin D2 e D3 + epimer Metil Malonic Acids Homocysteine Hepcidine Aminoacids

Xevo TQD

Toxicology and Forensic DOA in urine Ethylglucorinide in urine

All the parameters performed on TQD plus: All steroids Ethylglucorinide in hair DOA in whole blood and hair

All the parameters performed on Xevo TQD plus: Steroids at pediatric levels (estradiol/aldosterone) 1,25 (OH)2 Vitamin D3/D2 Ethylglucorinide on hair DOA in hair

All of these analysis are performed with one source:

ESCI®

Newborn Screening Panel: Newborn Screening Second tier test in DBS:

CAH hyperplasia (steroids) MMA, Hcy and propionic acid Lysosomial disorders oxisterols, sphingolipids

Xevo TQ-S micro

©2015 Waters Corporation 17

3988 Pichini S et al Journal of Pharmaceutical and Biomedical Analysis 118 (2016) 9–16 antidepressant and anxiolytic drugs

3989

Toyo’oka T & Kikura-

Hanajirib R Chem. Pharm. Bull. 63, 762–769 (2015) Synthetic Canabinoids

3990 Liang S-H Restek Apps Note Nicotine and Related Compounds

3991 Hodson L et al J Am Heart Assoc. 2015;4:e002258 Cortisol, DHEA, ASD

3992 Slominski AT et al doi:10.1111/exd.12872 Vitamin D3 metabolites

3993 Johnson JS et al 720005509en (October 2015) Thyroglobulin

3994 Li Y et al Journal of Chromatography A, 1409 (2015) 277–281 Metabolome, Lipidome

3995 Schlittenbauer L et al Journal of Chromatography A, 1415 (2015) 91–99 Matrix effects in human urine analysis

3996 Zhou Y et al Journal of Chromatography B, 976–977 (2015) 78–83 remimazolam and its metabolite

3997 Nye LC et al Bioanalysis (2015) 7(6), 643–652 metabolite of tenofovir disoproxil fumarate

3998 Leonart LP et al Bioanalysis (2015) 7(12), 1419–1422 metabolite id

3999 Meng X et al Anal. Methods, 2015, 7, 675–683 fluoroquinolone antibiotics

4000 Meijerink J et al British Journal of Pharmacology (2015) 172 24–37 Eicosanoids

4001 Wang X et al Forensic Toxicol DOI 10.1007/s11419-015-0285-6 GHB and GHB glucuronide

4002 Shintani-Ishida K et al Forensic Toxicol (2015) 33:348–354 4-MeOPBP

4003 Wang C-H et al Heart Vessels DOI 10.1007/s00380-015-0702-0 p-cresyl sulfate

4004 Cháfer-Pericás C et al Analytica Chimica Acta 886 (2015) 214-220 lipid peroxidation biomarkers

4005 Choi JY et al Additives & Contaminants: Part A, 32:7, 1029-1039, DOI: 10.1080/19440049.2015.1040080 narcotic adulterants

4006 Masubuchi N et al http://dx.doi.org/10.1016/j.cbi.2015.08.016

Oxidative stress markers, secondary bile

acids and sulfated bile acids

4007 Andersson M et al Forensic Science International 252 (2015) 150–156 Opioids

4008 Pechlivanis A et al DOI: 10.1021/acs.jproteome.5b00470 Human Urinary Metabolome

4009 Wang X et al J. Proteome Res. 2015, 14, 2849−2862

Metabolic Profiling of Age-Related

Mitochondrial Dysfunction

4010 Bolechová M et al Chem. Listy 109, 305-312 (2015) (Czech) Isoprostanes

4011 Bashaw S et al SOFT 2015 (Atlanta GA) Basic, Acid, and Neutral Drugs

4012 Chindarkar NS et al doi:10.1093/jat/bkv057 Tof vs tandem

4013 Henderson CM et al doi:10.1373/clinchem.2015.244541 Vitamin D Binding Protein

4014 James L et al PLOS ONE | DOI:10.1371/journal.pone.0131010 Bile Acids

4015 Xie G et al J. Proteome Res. 2015, 14, 850−859 Bile Acids

4016 Belul N Thesis (June 2015) Oxytocin

4017 Bronsema KJ et al Bioanalysis (2015) 7(1), 53–64 Nanobody

4018 Linder C et al Bioanalysis (2015) 7(16), 2031–2039 carbamazepine, lamotrigine and valproic acid

4019 Kozlovich S et al DOI: 10.1021/acs.chemrestox.5b00278 Tobacco-Specific Nitrosamine, NNAL

4020 Ehling S & Reddy TM J. Agric. Food Chem. 2015, 63, 7567−7573 leucine and metabolites

4021 Boccard J et al Bioanalysis (2014) 6(19), 2523–2536 Steroid metabolites

4022 Abbassi-Ghadi N et al DOI: 10.1007/s13361-015-1278-8 Lipidomic Profiling of h cancer tissue

4023 Burch TC et al PLOS ONE | DOI:10.1371/journal.pone.0134206 Metabolomic and Lipidomic Analysis

4024 Lang LM & Linnet K http://dx.doi.org/10.4172/2157-7145.1000189 Cortisol

4025 Daan NMP et al doi:10.1093/humrep/dev195 Androgens

Waters Application notes list: More than 4000 clinical application notes!