Final ProgramCPSA 2011
Science and Technology Coming Together to Make a Difference
October 3 - 6, 2011
Bucks County Sheraton Hotel
Langhorne, PA
Poster Abstract #21
Simultaneous Determination of Metabolic Stability, Metabolite Identification and Profiling Using the Agilent 6550 iFunnel Q-TOF LC/MS System
Agilent Technologies, Inc., Santa Clara, CA, US
Timely and rapid assessment of metabolic stability, metabolite identification and profiling is critical for accelerating lead optimization and enhancing the success rate of drug candidates entering into drug development. Triple quadrupole LC/MS instruments using multiple-reaction-monitoring (MRM) have been the workhorse for quantitative analysis such as metabolic stability and profiling. However, this platform is optimized for high sensitivity target quantitation and not well suited for non-targeted qualitative analysis. For these reasons, metabolite identification (qualitative) is often performed in a separate analysis on different types of mass spectrometers. Furthermore, due to the limitation of sensitivity on traditional tandem mass spectrometers, a relatively high substrate concentration (i.e.10-20 µM) is often required in order to identify metabolites with a broad coverage. The ability to obtain quantitation and identification in a single analysis makes metabolic stability, metabolite identification and profiling studies much more efficient. This also has the potential to increase assay productivity and decrease costs in drug discovery and development.
Herein, we present an integrated Qual/Quan workflow. The utility of the Agilent 6550 iFunnel Q-TOF LC/MS system for determination of metabolic stability, metabolite identification and profiling in a single experiment is demonstrated in the in vitro buspirone (1µM) metabolism study in rat liver microsomes.
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