title: Biotransformation of a new synthetic retinoid, 4-[(5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (Am-80), in the rat. Structure elucidation of the metabolites by mass and nmr spectrometry.
abstract: 1. The major metabolites of Am-80 in rat bile were examined by tlc-radiochromatography and hplc-radiochromatography after the intravenous administration of 14C-Am-80, and > 15 metabolites were detected. 2. Intact and Glusulase-treated bile were analysed by both tlc-radiochromatography and hplc-radiochromatography. As both samples gave similar patterns in both chromatography systems, we have concluded that neither glucuronide nor sulphate conjugates were present. 3. 2H3-Am-80 and 2H6-Am-80 were administered to rats, and the major metabolites in bile were detected and their structures elucidated by GC-MS. 4. The chemical structures of seven major biliary metabolites, including unchanged Am-80, were identified by mass and two-dimensional nmr spectrometry, and included 6-hydroxy-Am-80 (M-3), 7-hydroxy-Am-80 (M-4), 6-oxo-Am-80 (M-5), unchanged Am-80 (M-0) and the taurine conjugates of M-3 (M-1), M-4 (M-2) and M-0 (M-6).
authors.affiliation: Developmental Research Laboratories, Shionogi & Co. Ltd, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Mizobuchi
authors.forename: T
authors.initials: T
authors.lastname: Kuroda
authors.forename: H
authors.initials: H
authors.lastname: Okabe
authors.forename: K
authors.initials: K
authors.lastname: Mizojiri
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: J
authors.initials: J
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Terui
mesh_terms: D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D001565:Benzoates; D013764:Tetrahydronaphthalenes; C061133:tamibarotene