LC-MS/MS Solutions for Toxicology and Clinical Research

La spectrométrie de masse en tandem est devenue un outil essentiel pour les applications cliniques et la recherche biomédicale impliquant l’analyse de biomarqueurs. Contrairement aux méthodes classiques de dosage immunologique, l’analyse par chromatographie liquide couplée à la spectrométrie de masse (LC-MS/MS) permet une analyse très sélective et spécifique de composés multiples en un seul passage, conduisant à une plus grande confiance dans les résultats et permettant de nouvelles découvertes. La LC-MS/MS est idéalement adaptée pour identifier les hormones stéroïdes, la vitamine D et ses métabolites, des peptides ou des protéines et d'autres composés dans des matrices complexes tels que le sang, l'urine, la salive et les lysats céllulaires. Aujourd'hui, la LC-MS/MS est également la méthode préférée de l'analyse médico-légale surpassant les techniques d'analyse traditionnelles - à la fois à des fins de dépistage et de confirmation.

Cette présentation vous présentera comment SCIEX pourrait contribuer à améliorer le monde dans lequel nous vivons en permettant aux scientifiques et aux analystes de laboratoire de trouver des réponses aux défis analytiques complexes auxquels ils sont confrontés.

1. LC-MS/MS Solutions for Toxicology and Clinical Research by Aymeric Morla Senior Solutions Specialist Clinical Research, Clinical Diagnostics & Forensics South EMEA For research use only. Not for use in diagnostic procedures . RUO-MKT11-3115-A

2. Vision SCIEX Answers for Science. Knowledge for Life.™ Mission Provide integrated, reliable analytical tools to advance scientific understanding and safeguard health. Placing the power of life-changing answers into the hands of those who care, everywhere.

3. Pharma & Biopharma Clinical Research Forensics Food & Environment 3 Life Science Research 2 The Markets W e S erve Biologics Discovery & Development Small Molecule Discovery & Development Proteomics Metabolomics Lipidomics Clinical Research Contaminations & Safety Quality & Authenticity Water & Soil Testing Toxicology Forensics Clinical Research 4 1 2 3 Services & Support for Every Customer 4 1

4. No. 1 LC-MS/MS Provider for Over 2 Decades Trusted partner focused on exceeding your expectations Continuous investment in award-winning innovations  More than 20 new products since 2012  650 + issued patents or pending applications, 5+ issued patents/month  5 awards in 2014 alone Solutions that address your entire workflow  Complete portfolio of LC/MS, CE/MS solutions including methods, reagents, software and service Partnerships to advance scientific excellence  Partner with innovators and industry leaders such as; the Institute for Systems Biology, Illumina, Phenomenex , Gerstel USA and Beckman Coulter Best-in-class global service and support  More than 700 application, service and support associates deployed Worldwide  Over 300 training classes available online and in person

5. In the Netherlands, researchers use our CESI 8000 system for metabolomic profiling to gain insights into solving the mysteries of kidney disease. Horse racing officials turn to the QTRAP ® technology coupled with our M icroLC to identify performance enhancing hormones . Enabling Our C ustomers to Find A nswers In Singapore, researchers use SWATH ® A cquisition to identify biomarkers for inflammation of the eye. Investigators in Japan use our TripleTOF ® system to increase crop yields .

6. Our History — Over 40 Years of Innovation 1973 F ounded by Dr. Barry French and others at the University of Toronto 1981 D elivers the first commercial triple quadrupole MS/MS instrument 1989 Introduced API III, the first commercial dedicated LC/MS/MS system, creating the gold standard 2001 Launched API 4000 LC/MS/MS systems becomes the de facto standard for bioanalysis 2002 Released QTRAP ® which combines triple quad and linear ion trap for the first time 2005 Introduced API 5000 which was the most sensitive triple quadrupole system 2008 Launched the 5500 series which was the most advanced systems of the time 2010 Became a Danaher Corporation operating company and acquired the Eksigent LC business 2012 Launched the highest number of new products in the history of the company in a single year 2013 Launched first Medical Device and IVD solution and added Beckman CE to portfolio 2014 Partnered with Illumina creating the first multi- omics cloud-computing environment

7. SCIEX TripleTOF ® systems SCIEX Triple Quad ™ & QTRAP ® systems 3500 Series 4500 Series 5500 Series & SelexION 6500 & SelexION 4600 5600 + & SelexION Pushing the limits MicroLC M3 TM 6600 & SelexION 6500+ & SelexION + ExionLC TM Solutions LC-MS/MS SCIEX   X500R QTOF

8. Creating Complete Solutions For Routine Analysis Harnessing the power of Tandem MS : Best-in-class hardware + Easy to use software + Customizable applications solutions Get customers up and running quickly Market Specific Solution Hardware Unique QTRAP ® & QQQ Technology Best in Class UHPLC Software Cliquid® Software ChemoView ™ Software iMethod ™ Applications Specific methods for research use MRM Catalogues and Libraries Customer Support Installation and t raining Phone/On-site application support

9. Advantages of LC-MS/MS Greater selectivity and specificity Sensitivity Simplified sample preparation Short run times Multiple compound classes can be analyzed in a single run Inexpensive per sample costs

10. Ideal for any routine quantitative analysis Secure user-logon Simplified work-flow Preconfigured methods MRM catalogues Simplified data analysis tool Simplified reporting tool based on Microsoft word with range of pre-configured reports Available in English, Japanese and simplified Chinese by default. A dditional languages will be available separately. Cliquid ® Software and iMethod ™ Applications

11. Cliquid ® Software for Routine Analysis For research use only. Not for use in diagnostic procedures.

12. Homocysteine in Serum Testosterone in Plasma 1,25-Dihydroxyvitamin D3 in Plasma Antiretrovirals in Serum Metanephrines in Urine and Plasma Amino Acids in Urine, Plasma, CSF Forensic Drug Screening in Blood, Plasma, Urine Steroids in Serum EthylSulfate & EthylGlucuronide in Urine Benzodiazepines in Urine Forensic Drug Quantitation in Blood, Plasma, Urine Examples of Clinical Research and Forensic Applications For research use only. Not for use in diagnostic procedures.

13. Chromatogram of QC Control at 1.36 μg /mL iMethod ™ Applications – Homocysteine in Serum For research use only. Not for use in diagnostic procedures.

14. iMethod ™ Applications – Testosterone and low levels iMethod ™ Application for low testosterone level v1.0 Testosterone method designed for samples on the 5500 systems iMethod ™ Application for testosterone v1.0 Testosterone screening method for samples using the 3200 systems Testosterone 30 ng/mL Quality Control and D3-Testosterone (IS) 3200 QTRAP® with a Shimadzu Prominence LC system in a 3 minute run Quantifier Qualifier Int. Std. For research use only. Not for use in diagnostic procedures.

15. iMethod ™ Applications – Anti- retrovirals in Serum For research use only. Not for use in diagnostic procedures. Overlaid MRM ion traces for the Mid QC quantifier, qualifier, and internal standard transitions performed on a 3200 QTRAP ® LC-MS/MS system.

16. iMethod ™ Applications – Metanephrines in Urine and Plasma For research use only. Not for use in diagnostic procedures. Figure shows a representative chromatogram for Calibration Standard 4 (at a concentration of 100 pg /mL for each analyte ) in the plasma matrix method.

17. Key features: 45 physiological amino acids 18 minute run time Good correlation with traditional AAA techniques CV’s 5-10% For use with Plasma, Urine, CSF iMethod ™ Applications - Amino Acids Analysis For research use only. Not for use in diagnostic procedures. RUO-MKT-18-1999

18. ILeu Leu Ala Beta Ala Sar Separation of key AA 45 Physiological AA standards at 25 pmole on column on an API 3200™ System Example Amino Acids Chromatogram For research use only. Not for use in diagnostic procedures.

19. A Allo Isoleucine in plasma Ile Leu Nle All isomeric/isobaric AA’s resolved well GABA  ALA Sar ALA  Aib  Aba Val Nval Ile Leu Nle 1MHis 3 MHis All Isomeric/Isobaric Amino Acids Resolved For research use only. Not for use in diagnostic procedures.

20. Q1 Q3/LIT Q2 Q0 QJet Ion Rail of the SCIEX QTRAP ® 4500 System Key features: Screen for > 300 drugs 15 minute run time Confirmation by library search Library of over 1250 Drugs For blood, urine, saliva and tissue Via iMethod ™ Applications iMethod ™ Applications - Forensic Drug Screening For research use only. Not for use in diagnostic procedures.

21. 700 Forensic Drugs Screening with the 3200 QTRAP® LC/MS/MS System Comprehensive Forensic Drugs Screening For research use only. Not for use in diagnostic procedures.

22. iMethod ™ Applications – Benzodiazepines For research use only. Not for use in diagnostic procedures. Representative chromatogram of spiked urine at 20ng/mL performed on a 3200 QTRAP® LC-MS/MS system in a 8 minutes run.

23. iMethod ™ Applications – EthylSulfate & EthylGlucuronide in Urine For research use only. Not for use in diagnostic procedures. Sample chromatogram of MRMs of EtG and EtS detected at 100 ng/mL in a human urine sample.

24. iMethod ™ Applications – Forensic Drug Quantitation – Short Panel For research use only. Not for use in diagnostic procedures. Example chromatogram for Forensic drugs (short panel) generated on a 3200 QTRAP® system with a in a 6.6 minutes run.

25. sciex.com For more information

26. CONTACT US: Aymeric Morla, email: [email protected] AB Sciex is doing business as SCIEX. © 2010-2015 AB Sciex. The trademarks mentioned herein are the property of the AB Sciex Pte. Ltd. or their respective owners. AB SCIEX™ is being used under license. Beckman Coulter® is being used under license. For research use only. Not for use in diagnostic procedures. RUO-MKT11-3115-A