Characterization of In Vitro Metabolites of CP 47,497, a Synthetic Cannabinoid,in Human Liver Microsomes by LC‐MS/MS

CP 47,497, a potent cannabinoid receptor type 1 agonist, is the main active ingredient in the herbal mixture “Spice” sold in European countries. The illegal use of “Spice” for its psychoactive effects has become a social issue. In this study, the in vitro metabolism of CP 47,497 was investigated in human liver microsomes to characterize the metabolic fate of CP 47,497. CP 47,497 was incubated with human liver microsomes, and the reaction mixture was analyzed using liquid chromatography‐tandem mass spectrometry. A total of eight metabolites were detected in human liver microsomes and structurally characterized based on mass spectral data. The main metabolic pathways involved hydroxylations or oxygenations. The identified metabolites were mono‐oxygenated metabolites (M1 and M4), mono‐hydroxylated metabolites (M3, M5, M6, M7, and M8), and a di‐oxygenated metabolite (M2). The detection of these metabolites could confirm the presence of CP 47,497 in biological samples; therefore, collectively, they would be excellent indicators of “Spice” drug abuse.