Quantitative-qualitative data acquisition using a benchtop Orbitrap mass spectrometer.

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.