Structural determination of rat urinary metabolites of sodium 2-(4-(2-oxocyclopentylmethyl)phenyl)propionate dihydrate (loxoprofen sodium), a new anti-inflammatory agent.

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Abstract
The main metabolites of loxoprofen sodium were isolated from rat urine by column chromatography. Their chemical structures were determined on the basis of spectral data and by comparison of the metabolites with authentic samples as follows: the parent acid (M-0); 2 reduction products, i.e., the cis-alcohol (M-1) and the trans-alcohol (M-2); the .alpha.-hydroxy ketone (M-3); and 3 diol metabolites (M-4, M-5 and M-6). The established metabolite structures indicated that metabolic reactions of loxoprofen in rats occur only at the cyclopentanone moiety. The trans-alcohol metabolite, which has a high inhibitory activity on prostaglandin (PG)-synthetase, was optically pure, with (2S, 1''R, 2''S)-configurations, by high performance liquid chromatography (HPLC) analysis after derivatization to the diastereomeric amide of the carboxy group with (-)-.alpha.-phenylethylamine reagent and subsequently to the ester of the hydroxy function using (-)-.alpha.-methoxy-.alpha.-trifluoromethylphenylacetyl chloride.