Identification of phase I and phase II metabolites of ketobemidone in patient urine using liquid chromatography–electrospray tandem mass spectrometry

Ketobemidone and five of its phase I metabolites were identified in the urine of four patients post intravenous administration of Ketogan Novum^®. Furthermore, indications of the presence of the glucuronide conjugates of ketobemidone and norketobemidone is presented. Both hydrolyzed (β-glucuronidase) and unhydrolyzed human urine was extracted on a mixed-mode slightly polar cation-exchange SPEC cartridge prior to analysis with LC–ESI-MS–MS. The phase I metabolites were identified by comparison of their daughter spectra with those of synthesized standards. The glucuronides were identified by their molecular mass and interpretation of the daughter spectra, as no standards were available for these compounds.