Identification of fentanyl metabolites in rat urine by gas chromatography-mass spectrometry with stable-isotope tracers.
The metabolites of fentanyl (l), which has been widely used as a neuroleptic analgesic agent, were identified in urine of rats by gas chromatography-mass spectrometry combined with a stable-isotope tracer technique. After the oral administration of an equimolar mixture of l and deuterium-labeled l (l/l-d5), the urinary metabolites were extracted with chloroform at pH 9.0. Extracts were derivatized and analyzed by GC/MS. Metabolites were identified by the presence of doublet ion peaks separated by 5 amu, and chemical structures were established from analyses of fragmentation pathways. The metabolites were identified as 4-N-(N-propionylanilino)-piperidine, 4-N-(N-hydroxypropionylanilino)piperidine, 4-N-(N-propionylanilino) hydroxypiperidine, 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-propionylanilino)hydroxypiperidine. These metabolites, together with unchanged l, were also detected in urine of rats receiving l/l-d5 intravenously, by selected-ion monitoring of the specific cluster ions.
D000818:Animals; D001711:Biotransformation; D003903:Deuterium; D005283:Fentanyl / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003903:Deuterium; D005283:Fentanyl