Identification and Quantitative Determination of Fentanyl Metabolites in Patients by Gas Chromatography-Mass Spectrometry

Abstract

Although fentanyl has been used widely as a short-acting narcotic analgesic, its metabolism in humans has not been clarified. In this study, 3 fentanyl metabolites were identified in the urine of 8 surgical patients receiving 0.3-0.5 mg of fentanyl i.v. The metabolites 4-N-(N-propionylanilino)piperidine, 4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine, and unchanged fentanyl were identified by gas chromatography-mass spectrometry in urine collected 6 h after administration. Fentanyl and its main metabolite, 4-N-(N-propionylanilino)piperidine, were determined quantitatively in the urine of 5 additional patients receiving 0.5 mg fentanyl i.v. Urinary excretion of fentanyl and 4-N-(N-propionylanilino)-piperidine during the first 12 h after injection accounted for 0.3-4.0% and 26-55% of the dose, respectively.