Metabolism of Fentanyl in Isolated Hepatocytes from Rat and Guinea Pig

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The metabolites of fentanyl (FT) were identified in isolated rat and guinea pig hepatocytes by gas chromatography-mass spectrum (GC-MS) combined with the stable isotope tracer technique. Isolated hepatocytes were prepared by the collagenase perfusion method and were incubated with a 0.3mM equimolar mixture of FT and FT-d₅ citrate in a rotating round-bottomed flask at 37°C. The metabolites were extracted with chloroform. The extracts were subjected to GC and GC-MS after trimethylsilylation. Characteristic doublet peaks in the mass spectra indicated the presence of 6 and 7 metabolites in rat and guinea pig hepatocytes, respectively. 4-(N-Propionylanilino) piperidine was identified as the main metabolite in both species. Other metabolites were oxidation products of the phenethyl, piperidine and propionyl groups of FT. Oxidation of the anilino ring and hydrolysis of the amide bond were not found in hepatocytes.