Identification of enzymes responsible for the metabolism of a drug is critical in evaluating drug interactions and potential PK variation due to the involvement of phenotypic variation in CYPs.Ideally,metabolites with corresponding metabolic pathways should be identified and used for quantitation in enzyme kinetic studies at clinically relevant concentrations.However,in early drug discovery,substrate depletion is commonly used for these studies because traditional metabolite identification and synthesis is time and resource consuming.The main advantage of hybrid QTRAP mass spectrometry instruments over traditional quadrupole and ion trap instruments is the capability of obtaining both quantitative and qualitative data for metabolism studies in a single analysis.This feature is especially useful for low substrate concentration or low turnover kinetic studies including reaction phenotyping.