Identification of drug metabolites can often yield important information regarding clearance mechanism, pharmacologic activity, or toxicity for drug candidate molecules. Additionally, the identification of metabolites can provide beneficial structure-activity insight to help guide lead optimization efforts towards molecules with optimal metabolic profiles. There are challenges associated with detecting and identifying metabolites in the presence of complex biological matrices, and new LC-MS technologies have been developed to meet these challenges. In this report, we describe the development of an experimental approach that applies unique features of the hybrid linear ion trap Orbitrap mass spectrometer to streamline in vitro and in vivo metabolite identification experiments. The approach, referred to as MS(M), utilizes multiple collision cells, dissociation methods, mass analyzers, and detectors. With multiple scan types and different dissociation modes built into one experimental method, along with flexible post-acquisition analysis options, the MS(M) workflow offers an attractive option to fast and reliable identification of metabolites in different kinds of in vitro and in vivo samples. The MS(M) workflow was successfully applied to metabolite identification analysis of verapamil in both in vitro rat hepatocyte incubations and in vivo rat bile samples.