Quantitative-qualitative data acquisition using a benchtop orbitrap mass spectrometer |
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Authors: | Kevin P Bateman Markus Kellmann Helmut Muenster Robert Papp Lester Taylor |
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Institution: | aMerck Frosst Canada Ltd., Kirkland, Quebec, Canada;bThermo Fisher Scientific, Bremen, Germany;cThermo Fisher Scientific, San Jose, California, USA |
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Abstract: | Current approaches to discovery-stage drug metabolism studies (pharmacokinetics, microsomal stability, etc. ) typically use
triple-quadrupole-based approaches for quantitative analysis. This necessitates the optimization of parameters such as Q1
and Q3 m/z values, collision energy, and interface voltages. These studies detect only the specified compound and information about
other components, such as metabolites, is lost. The ability to perform full-scan acquisition for quantitative analysis would
eliminate the need for compound optimization while enabling the detection of metabolites and other non-drug-related endogenous
components. Such an instrument would have to provide sensitivity, selectivity, dynamic range, and scan speed suitable for
discovery-stage quantitative studies. In this study, a prototype benchtop Orbitrap-based mass analyzer was used to collect
both quantitative and qualitative data from human microsomal incubation samples as well as rat plasma from pharmacokinetic
studies. Instrumental parameters such as scan speed, resolution, and mass accuracy are discussed in relation to the requirements
for a quantitative-qualitative workflow. The ability to perform highly selective quantitative analysis while simultaneously
characterizing metabolites from both in vitro and in vivo studies is discussed. |
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