Hydantoin ring glucuronidation: characterization of a new metabolite of 5,5-diphenylhydantoin in man and the rat.

A new metabolite of 5,5-diphenylhydantoin has been found in human urine and in rat bile. This new metabolite arises by direct glucuronidation of 5,5-diphenylhydantoin (i.e. no prior aryl hydroxylation occurs) and is characterized as the N-3 glucuronide. This structure assignment is based on (a) study of mass spectra of permethyl, perdeuteriomethyl, N-methyl-per-O-deuteriomethyl and deuteriomethyl ester permethyl derivatives and (b) comparison of the reactions of the new glucuronide metabolite and 5,5-diphenyl-3-methylhydantoin with diazomethane. Prominent ions at m/e 322 and 378 in the mass spectrum of the permethylated derivative of the glucuronide metabolite arise via retro Diels-Alder reactions of the glycone ring.