Isolation and Identification of Three Major Metabolites of Retinoic Acid from Rat Feces

Following the intraperitoneal administration of high doses of 14C‐ and 3H‐ labelled retinoic acid (1) to rats, three major metabolites and the intact compound were isolated from the feces in microgram amounts by use of column, thin‐layer and high‐pressure liquid chromatography. Their structures were elucidated by mass spectrometry and Fourier Transform 1H‐NMR. spectroscopy as 2 (all‐trans‐4‐oxoretinoic acid), 3 (7‐trans‐9‐cis‐11‐trans‐13‐trans‐5′‐hydroxy‐retinoic acid). Hydroxylation of the 5‐methyl group of the cyclohexene ring, oxidation of the cyclohexene ring in position 4 and cis‐trans isomerisation of the nonatetraenoic acid side chain were the reactions, which produced these products from retinoic acid. The metabolites 2 and 4 each accounted for about 4% of the radioactivity administered. The metabolite 3 and the parent compound accounted for about 16% and 17% of the dose, respectively.