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 chromato-graphy 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).