HPLC-MS/MS in drug metabolism and pharmacokinetic screening.

During the lead optimization stages, one common requirement for many processes is the need for bioanalytical support. This review summarizes high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) methodologies that are employed in drug metabolism and pharmacokinetic screens for a series of new chemical entities. The HPLC-MS/MS methods for trace organic quantitative determinations to support both in vitro and in vivo experiments and for the qualitative assays, such as metabolite identification, are presented. The challenges of performing HPLC-MS/MS assays, such as the choice of ionization sources, matrix ionization suppression and the potential for endogenous interferences, are also addressed.