Isolation and Identification of Three Urinary Metabolites of Retinoic Acid in the Rat

After the intraperitoneal administration of high doses of 14C‐ and 3H‐labelled retinoic acid (1) to rats three major urinary metabolites have been isolated in microgram amounts by use of column, thin‐layer and high‐pressure liquid chromatography. Their structures were elucidated by mass spectroscopy and Fourier transform 1H‐NMR. spectroscopy as 2 (5‐methyl‐5‐[2‐(2,6,6‐trimethyl‐3‐oxo‐1‐cyclohexen‐1‐yl)vinyl]‐2‐tetrahydrofuranone), 3 (5‐[2‐(6‐hydroxymethyl‐2,6‐dimethyl‐3‐oxo‐1‐cyclohexen‐1‐yl)vinyl]‐5‐methyl‐2‐tetrahydrofuranone) and 4 (6‐(6‐hydroxymethyl‐2,6‐dimethyl‐3‐oxo‐1‐cyclohexen‐1‐yl)‐4‐methyl‐4‐hexenoic acid). In these metabolites the tetraene side chain of 1 is shortened and the cyclohexene ring oxidized. The radioactivity of 2 and 3 accounted for about 10% (0.9% of the dose) each, metabolite 4 for about 6% (0.5% of the dose) of the total urinary radioactivity.