Our laboratory has used the power of mass spectrometry (MS) coupled to liquid or gas chromatography to measure amounts of drugs, drug metabolites and other xenobiotics in biological samples. We often use this technology to provide analytical services to other investigators, either commercially or collaboratively. When funding for research is obtained, we have used MS techniques to study in vitro drug metabolism. This includes use of animal models, human liver microsomes, cDNA-expressed drug metabolizing enzymes and human clinical studies. We have examined the role of cytochrome P450s (CYP) 2D1 in rat metabolism of amphetamine, the involvement of different in CYPs in the metabolism of l-acetylmethadol (LAAM) and methadone, and the involvement of both CYPs and glucuronosyltransferases (UGT) in the metabolism of buprenorphine. Currently we are studying in vitro inhibition of the metabolism of oxycodone, methadone and buprenorphine.