DRUG METABOLISM Drug discovery & development solutions FOR DRUG METABOLISM

Fast and efficient metabolite identification is critical in today’s drug discovery pipeline. The goal is to achieve rapid structural identification and complete characterization of major and low-level metabolites in a single analysis. AB SCIEX triple quadrupole-linear ion trap mass spectrometers and accurate mass approaches make that goal a reality. – Qual & Quant for the answers you need: Get high-sensitivity quantification and new qualitative capabilities on a single platform—the AB SCIEX TripleTOF™ 5600 System and MetabolitePilot™ Software. – Fast and efficient low-level metabolite identification:...

Simple, clear metabolism workflows MetabolitePilot™ Software deliver high sensitivity quantification and new qualitative capabilities on a single platform. The AB SCIEX QTRAP® 5500 and LightSight® Software use predictive MRM (pMRM) and multiple precursor ion and/or neutral loss survey scans in a single analysis, including polarity switching. AB SCIEX TripleTOF™ 5600 System AB SCIEX QTRAP® 5500 System Accurate mass at the speed and sensitivity of a triple quadrupole: A single platform for drug metabolism and bioanalytical The AB SCIEX TripleTOF™ 5600 System and Fast MS and MS/MS acquisition speeds...

Drug discovery & development pipeline Metabolite identification is central to many of the activities in the discovery and development pipeline. From rapid structural identification during the discovery process to provide an early perspective on the metabolically labile sites, or soft spots of a drug candidate, to a more complete characterization of the metabolic clearance process to maximize safety and efficacy, there’s an ever-increasing demand on throughput. The ability to find, identify and confirm metabolites as fast as possible is critical; not only for the major metabolites, but the very...

Early discovery: metabolic stability screening Metabolic stability assessment Take soft-spot analysis to new levels of speed, efficiency and depth of data with the TripleTOF™ 5600 and MetabolitePilot™ Software. Apply completely generic methodology to acquire high quality quantitative and qualitative data simultaneously for soft-spot analysis. The AB SCIEX TripleTOF™ 5600 System makes it possible, with TOF MS and MS/MS scanning at rates suitable for UPLC • Generate quantitative data on the parent compound from the • Automatically acquire MS/MS data on the major metabolites using high-speed IDA...

Early discovery: reactive metabolite detection Detect low-level reactive metabolites in complex samples using glutathione (GSH) detection with the AB SCIEX QTRAP® 5500 System and LightSight® Software. The formation of undetected reactive metabolite species can potentially cause idiosyncratic adverse drug reactions (lADRs), which can lead to Black Box warnings and withdrawal of drugs from the market. GSH detection is one of the most sensitive ways of detecting low-level, transient reactive metabolites in complex biological samples. Total cycle time 2 Survey scans with polarity switching in 1 injection...

Late stage discovery: In vivo metabolite identification Identify metabolites of lead drug candidates for structural elucidation using selective detection techniques such as mass defect filtering with the TripleTOF™ 5600 System. For the first time, multiple mass defect filters can be applied in real time to select peaks for MS/MS data acquisition. There is no need to schedule a second injection to obtain MS/MS information. With the TripleTOF™ 5600 you can detect and characterize major metabolites in vivo with a single injection. A Minor oxidative metabolite (2.59 minutes) of Carbamazepine detected...

Late stage discovery: In vivo detection in complex matrices Detect low levels of metabolites at clinically relevant concentrations in vivo—even in matrices such as bile, plasma, urine and feca extracts—using the QTRAP® 5500 System. The predictive MRM (pMRM) survey method on the QTRAP® 5500 System is the most sensitive and selective single-injection strategy for identifying metabolites in challenging matrices XIC ol +MRM (176 pairs): E*p 1, 219 0/194 1 Da from Sample 5 [R5-T=60 ejaama-eonc) of Concplasma_pMRM_04MAR09A mtf (Tur.. Low level in vivo metabolite detection in protein precipitated metabolites...

Development: definitive in vivo metabolite ID Metabolite characterization in lead compounds Acquire accurate mass data for both parent and fragments in lead compounds with the TripleTOF™ 5600 System and MetabolitePilot™ Software. An advanced collision cell design and collision energy spread function produce rich MS/MS fragmentation in the low mass range for structure elucidation. Rich fragmentation, high resolution and mass accuracy enable definitive metabolite profiling. Hydroxymidazolam in rat liver microsomes. Excellent accuracy and resolution at the low mass range in MS/MS enables unambiguous...

integrated qual/quant workflows Metabolite quantification Estimate metabolite concentrations, without a reference standard, using mass extracted ion chromatograms from high-resolution experiments using the TripleTOF™ 5600 System, MetabolitePilot™ Quantification of metabolites and cross-species quantitative comparisons have received greater emphasis due to the Metabolites in Safety Testing (MIST) Guidelines. Estimating metabolite concentrations without a reference standard, however, is challenging TripleTOF™ 5600 System, MetabolitePilot™ and MultiQuant™ Software meets the challenge by enabling...

Biotransformation studies Acquire and process mass spectrometric and UV or radiochromatographic data in the same experiment with the QTRAP® 5500 System and LightSight® Software—and without time-consuming manual procedures. All together now: Correlation of UV and MS data of rat liver microsomal metabolites of Bromocriptine. The Processing Workspace of LightSight® Software makes the correlation of UV absorbance, pMRM, and EPI-MS/MS data easy and intuitive.