Thermo Scientific PAiNACEA Suite of Solutions

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m a s s s p e c t r o m e t r y Thermo Scientific PAiNACEA Suite of Solutions LC-MS Solutions for Pain Management Analysis in Forensic Toxicology Laboratories Benzodiazepines Opiates Synthetic Opioids Alcohol Biomarkers Medical Drugs of Abuse Part of Thermo Fisher Scientific

Pain management drugs and drugs of abuse analysis optimized for forensic toxicologists The Thermo Scientific PAiNACEA suite of solutions is a complete set of integrated liquid chromatography-mass spectrometry (LC-MS) systems optimized for qualitative and quantitative analyses of benzodiazepines, opiates, synthetic opioids, alcohol biomarkers and medical drugs of abuse in forensic toxicology. The PAiNACEA suite of solutions maximizes sample throughput, improves turnaround time and reduces overall analysis cost, without compromising data quality. 2Thermo Scientific PAiNACEA Suite of Solutions Pain management drugs are thermally labile, polar compounds highly amenable to LC-MS analysis. They ionize easily with either atmospheric pressure chemical ionization (APCI) or electrospray ionization (ESI), and can be detected and quantified by the mass spectrometer at low concentrations in biological matrices with impressive sensitivity and specificity. LC-MS offers unsurpassed speed and accuracy compared to traditional analytical techniques. You can screen, confirm and quantitate using a single analytical system and in many cases a single analytical run. The technology enables easy expansion of testing panels to accommodate analysis of not only more target drugs, but also their metabolites, without going through extensive method development or waiting for the latest immunoassay tool. For analyzing a wide array of pharmacologically important drugs and their metabolites in complex biological matrices in less time, LC-MS is the technology of choice. This PAiNACEA system is equipped with the Thermo Scientific Transcend TLX system coupled with the Thermo Scientific TSQ Quantum Access MAX triple stage quadrupole mass spectrometer. We offer expandable LC systems to meet your forensic laboratory s budget and throughput needs, from ultrahigh pressure liquid chromatography (UHPLC) to automated online sample preparation and multiplexing. Couple this with our industry-leading triple stage quadrupole mass spectrometer or our state-of-the-art ultrahigh resolution accurate mass (HRAM) high performance benchtop mass spectrometer and you have the best-in-class LC-MS solution right out of the box. Our dedicated team of specialists will help you determine which PAiNACEA solution is best suited to your workflow.

The PAiNACEA system helped us increase our sample throughput by multiplexing four LC channels without sacrificing the selectivity or sensitivity of the triple stage quadrupole mass spectrometer. Bridget Crews, Ph.D., Scientific Director at Millenium Laboratories Fully integrated and expandable LC-MS systems Tailored to budget and throughput requirements Ready-to-go, performance-verified methods World class product support Flexible, comprehensive financing options 3

Improve Productivity with Liquid Chromatography The PAiNACEA suite of solutions offers a choice of Thermo Scientific LC systems to provide forensic laboratories with features to increase analytical flexibility, reliability and productivity. Whether you need dilute-n-shoot, multiplexing or automated online sample preparation, our LC systems are perfectly matched to our mass spectrometers to achieve shorter run times, increase sample throughput and attain superior data quality. Expand Method Flexibility Minimize Sample Preparation 4Thermo Scientific PAiNACEA Suite of Solutions Liquid-Liquid Extraction (LLE) 1. Aliquot of sample 2. Spike with IS 3. Add buffer 4. Add MTBE 5. Shake 10 min 6. Centrifuge 7. Remove organic 8. Evaporate to dryness 9. Reconstitute 10. Transfer to plate 11. Inject onto column The Thermo Scientific Accela LC system supports dilute-n-shoot, crash-n-shoot, SPE, PPT and LLE protocols. The flexible Accela system offers HPLC and UHPLC in one quaternary unit with operating pressures up to 1250 bar. This modular system can also be upgraded to the Thermo Scientific Transcend TLX system for even higher sample throughput. TurboFlow technology minimizes sample preparation. Solid Phase Extraction (SPE) 1. Aliquot of sample 2. Spike with IS 3. Add 0.1N HCL 4. Condition sorbent 5. Add sample to sorbent 6. Wash 7. Evaporate 8. Reconstitute 9. Transfer 10. Inject onto column Increase Sample Throughput The Transcend TLX system offers a unique multiplexing technology bringing the productivity of up to four separate, parallel LC systems to a single mass spectrometer. Run a single method or multiple methods simultaneously to ensure ensuring the maximum utilization of your mass spectrometer. You can significantly boost productivity without compromising data quality or sensitivity. The Transcend TLX system also offers Thermo Scientific TurboFlow technology an automated online sample preparation technique for complex matrices for the mass spectrometer. By combining the principles of turbulence, diffusion and chemistry, TurboFlow technology quickly separates target analytes from biological fluids prior to analysis by mass spectrometry. TurboFlow methods are ideal for laboratories wishing to reduce time performing sample preparation. Protein Precipitation (PPT) 1. Aliquot of sample 2. Spike with IS 3. Add acetonitrile 4. Centrifuge 5. Remove supernatant 6. Reconstitute 7. Transfer to plate 8. Inject onto column Autosampler LC Pumps LC Pumps LC Pumps LC Pumps TurboFlow Method 1. Aliquot of sample 2. Spike with IS 3. Centrifuge 4. Inject onto column Parallel System, Serial Data Column Column Column Column Mass Spectrometer The Transcend TLX-4 system is a multiplexed HPLC solution with four independent, parallel channels.

Resolve Complexity with Mass Spectrometry Laboratories around the globe count on Thermo Fisher Scientific, the world leader in serving science, to help solve their analytical challenges. With over 25 years of history in delivering breakthrough innovations in ion trap, triple stage quadrupole, and Thermo Scientific Orbitrap technologies, we provide an unmatched portfolio of mass spectrometer systems. Absolute Quantitation with Triple Stage Quadrupole Mass Spectrometry 1 Opiates 0 min 7 min With proven speed, specificity and low pg/ml sensitivity, triple stage quadrupole mass spectrometers are the instrument of choice for quantitative analysis of pain management drugs in forensic toxicology laboratories. When coupled with the Transcend TLX system, our triple stage quadrupole mass spectrometers can analyze benzodiazepines, opiates, synthetic opioids, alcohol biomarkers and medical drugs of abuse simultaneously and within minutes. The Thermo Scientific TSQ Quantum Access MAX triple stage quadrupole mass spectrometer is the ideal choice for the forensic toxicology laboratory. It offers simplicity, versatility, best-in-class performance capabilities and value. 2 3 4 Resulting Data Benzodiazepines 0 min 5.5 min Opiates 0 min 7 min Benzodiazepines 0 min 5.5 min Simultaneous analysis of benzodiazepines and opiates using the PAiNACEA system including a triple stage quadrupole mass spectrometer resulting in increased throughput up to 400%. Analyte R2 (1/x weighing) Range (ng/ml) LOD (ng/ml) 7 Aminoclonazepam 0.99 5-5000 1 Alpha-Hydroxyalprazolam 0.997 5-5000 1 Lorazepam 0.999 5-5000 1 Oxazepam 0.998 5-5000 1 Alprazolam 0.993 5-5000 1 Nordiazepam 0.99 5-5000 1 Clonazepam 0.996 5-5000 1 Morphine 0.9951 50-25000 25 Oxymorphone 0.9903 50-25000 1 Hydromorphone 0.995 50-25000 1 Codeine 0.9981 50-25000 1 Oxycodone 0.99 50-25000 1 Hydrocodone 0.888 50-25000 1 Dihydrocodeine 0.9993 50-25000 1 Labs can attain required limits of detection (LODs) and linear dynamic range, using the lowest cost PAiNACEA solution.

Unequivocally Identify with High Resolution Accurate Mass (HRAM) The Thermo Scientific Exactive high performance benchtop mass spectrometer is the latest addition to an industry-leading portfolio of mass spectrometers for forensic toxicologists. Powered by Orbitrap technology, the Exactive high performance benchtop LC-MS system is ideal for fast, unambiguous identification of drugs and their metabolites in complex mixtures. With exceptional mass accuracy measured up to the fourth decimal place, the Exactive easily resolves co-eluting isobaric interferences common to biomatrices. Taking advantage of HRAM full-scan mass-spectral data, you can screen, confirm and quantitate target and non-target compounds in a single analytical run. Minimal to no-method development time is required. And with HRAM, the data can then be retrospectively analyzed for compounds, without the need to re-inject your samples. Area Ratio 30 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 EtG 100-20,000 ng/ml Ethyl_Glucuronide Y = -0.0175482+0.00127676*X R^2 = 0.9907 W: 1/X^2 0 2000 4000 6000 8000 10000 12000 14000 16000 18000 20000 22000 0 5000 10000 15000 20000 ng/ml ng/ml Area Ratio 36 34 32 30 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 EtS 100-20,000 ng/ml Ethyl_Sulphate Y = -0.0105889+0.0014412*X R^2 = 0.9837 W: 1/X^2 The Exactive mass spectrometer resolves EtG and EtS from matrix in urine with HRAM (Data courtesy of Fortes Labs, Portland, Oregon) The beauty of the PAiNACEA system with the Exactive mass spectrometer is that it allows us to look for unknown metabolites at the same time that we quantitate known metabolites. In our laboratory, we have been able to identify four different fentanyl metabolites with no need for UV detection, fraction collection with NMR, or MS/MS fragmentation patterns. Uwe Christians, M.D., Ph.D., Professor, Department of Anesthesiology, University of Colorado and isis Clinical Research & Development Lab Director

PAiNACEA Solutions Backed by Worldwide Service and Support We understand the challenges you face: increasing productivity, reducing costs, achieving better results. Tap into our expertise throughout the life of your PAiNACEA system. Rest assured you are supported by a worldwide network of highly trained, certified engineers and scientists who are experts in forensic laboratory technologies and applications. Put our team of experts to work for you from system installation, training and technical support, to complete asset management and reagent leasing. As the world leader in serving science, Thermo Fisher Scientific has you covered. Performance-verified LC-MS methods Benzodiazepines and benzo-like substances Opiates and morphinomimetics Drugs of Abuse such as amphetamines, barbiturates, and cannabinoids Alcohol metabolites such as EtG and EtS The PAiNACEA suite of solutions increases laboratory productivity with your choice of: Dilute-n-shoot protocols: improves productivity by reducing consumables, time and labor. Multiplexing HPLC technology: increases method throughput up to four times using a single mass spectrometer. TurboFlow Technology: automated online sample preparation reduces sample preparation up to 95%. Selected Reaction Monitoring (SRM): available with our industry-leading triple stage quadrupole mass spectrometers, increases analytical speed, sensitivity and specificity. Ultrahigh resolution accurate mass (HRAM): full-scan mass-spectral information enables simultaneous qualitative and quantitative analyses of both knowns and unknowns. Methods for pain management drugs: performance-verified by our scientists and customers, reduce training time and ensure reliable, consistent results. 5

Laboratory Solutions Backed by Worldwide Service and Support Tap our expertise throughout the life of your instrument. Thermo Scientific Services extends its support throughout our worldwide network of highly trained and certified engineers who are experts in laboratory technologies and applications. Put our team of experts to work for you in a range of disciplines from system installation, training and technical support, to complete asset management and regulatory compliance consulting. Improve your productivity and lower the cost of instrument ownership through our product support services. Maximize uptime while eliminating the uncontrollable cost of unplanned maintenance and repairs. When it s time to enhance your system, we also offer certified parts and a range of accessories and consumables suited to your application. To learn more about our products and comprehensive service offerings, visit us at www.thermoscientific.com. In addition to these offices, Thermo Fisher Scientific maintains a network of representative organizations throughout the world. Africa-Other +27 11 570 1840 analyze.sa@thermo.com Australia +61 3 9757 4300 analyze.au@thermo.com Austria +43 1 333 50 34 0 analyze.at@thermo.com Belgium +32 53 73 42 41 analyze.be@thermo.com Canada +1 800 530 8447 analyze.ca@thermo.com China +86 10 8419 3588 analyze.cn@thermo.com Denmark +45 70 23 62 60 analyze.dk@thermo.com Europe-Other +43 1 333 50 34 0 analyze.emea@thermo.com Finland / Norway/Sweden +46 8 556 468 00 analyze.se@thermo.com France +33 1 60 92 48 00 analyze.fr@thermo.com Germany +49 6103 408 1014 analyze.de@thermo.com India +91 22 6742 9434 analyze.in@thermo.com Italy +39 02 950 591 analyze.it@thermo.com Japan +81 45 453 9100 analyze.jp@thermo.com Latin America +1 561 688 8700 analyze.la@thermo.com Middle East +43 1 333 50 34 0 analyze.emea@thermo.com Netherlands +31 76 579 55 55 analyze.nl@thermo.com New Zealand +64 9 980 6700 analyze.au@thermo.com Russia/CIS +43 1 333 50 34 0 analyze.emea@thermo.com South Africa +27 11 570 1840 analyze.sa@thermo.com Spain +34 914 845 965 analyze.es@thermo.com Switzerland +41 61 716 77 00 analyze.ch@thermo.com UK +44 1442 233555 analyze.uk@thermo.com USA +1 800 532 4752 analyze.us@thermo.com www.thermoscientific.com Thermo Fisher Scientific, San Jose, CA USA is ISO Certified. 2010 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific Inc. and its subsidiaries. Specifications, terms and pricing are subject to change. Not all products are available in all countries. Please consult your local sales representative for details. BR63274_E 01/11S