Technical Note: Simultaneous Qualitative And Quantitative Analysis Using The Agilent 6540 Accurate-Mass Q-TOF

By Pat Perkins, Anabel Fandino, Lester Taylor, Agilent Technologies, Inc.

The utility of the Agilent 6540 Accurate-Mass Q-TOF LC/MS System for the determination of metabolic stability, profiling, and identification in a single experiment has been demonstrated in a buspirone metabolic study, thus maximizing the quantitative and qualitative information that can be obtained from one experiment. The validity of the quantitative data was confi rmed by analysis using the Agilent 6460 Triple Quadrupole LC/MS System, operating in multiple reaction monitoring (MRM) mode.

Determining metabolic stability is an important aspect of early drug discovery, due to its role in drug half-life and bioavailability. Metabolite identification is crucial in order to understand drug safety and efficacy. In early drug discovery, samples are typically analyzed by a variety of different LC/MS methods in order to generate both metabolic stability (quantitative) and metabolite identification (qualitative) data. The ability to obtain both quantitation and identification in a single analysis makes metabolic stability, profiling, and identification studies much more efficient. The study described here demonstrates the use of the high resolution and accurate mass determination capabilities of the Agilent 6540 QTOF LC/MS to perform both quantitation and identification of metabolites in the same experiment.