( Chromatography and Mass Spect...)Analysis of a Verapamil Microsomal Incubation using Metabolite ID and Mass FrontierTM

Chromatography and Mass Spectrometry Application Note

Key Words Metabolism Study Structure Elucidation Metabolite ID Mass Frontier

Mark R. Kagan, Thermo Electron Corporation

Introduction
The characterization of a drugs metabolites plays a crucial role throughout its development. In the early discovery phase, studies are designed to help the medicinal chemist quickly identify metabolic hot spots that might require chemical modification in order to improve pharmacokinetics. At this early stage, the emphasis is typically on analyses with fast turnaround speeds, due to the large number of compounds involved. As the development process moves forward and the number of drug candidates is reduced, the emphasis shifts from speed to completeness, especially when regulatory and toxicity issues are involved. By the time a drug candidate reaches the latter stages of development, a team of scientists might spend years exhaustively characterizing its metabolic products.

LC/MS has become the technique of choice in these metabolism studies due to its inherently high level of sensitivity and specificity. In a typical analysis requiring less than one hour to complete, data sufficient to identify and characterize dozens of metabolites spanning a wide range of concentrations can be acquired. However, the information content in these LC/MS experiments can be extremely high, necessitating the need for efficient software tools. These software tools should satisfy the needs of both 1) the medicinal chemist in early stage discovery who must quickly screen large numbers of compounds for major metabolites and, 2) the needs of the researcher in late-stage development who must completely characterize all metabolites, including those present at very low levels. The Metabolite ID and Mass Frontier software packages have been designed to satisfy these diverse requirements.

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