Gas chromatographic-mass spectrometric studies on the metabolic fate of ethotoin in man
Bius, D.L.; Yonekawa, W.D.; Kupferberg, H.J.; Cantor, F.; Dudley, K.H.
Drug Metabolism and Disposition the Biological Fate of Chemicals 8(4): 223-229
1980
ISSN/ISBN: 0090-9556 PMID: 6105055 Document Number: 166620
Unchanged ethotoin and 11 metabolic products of ethotoin were detected in the urine of subjects (2 men and 1 woman) receiving ethotoin. Nine of these products were identified by comparison of their retention times and mass spectra with those of authentic synthetic samples. Hydroxylation of the hydantoin ring at the 5-position produced 5-hydroxyethotoin and 5-hydroxy-5-phenylhydantoin. Aryl hydroxylation resulted in the formation of p-hydroxyethotoin, o-hydroxyethotoin, m-hydroxyethotoin, 3-methoxy-4-hydroxyethotoin, and 3,4-dihydroxyethotoin. Most of these were excreted as the glucuronide conjugate. A dihydrodiol of ethotoin and 3-ethyl-5-hydroxy-5-(4-hydroxyphenyl)hydantoin were isolated along with unchanged ethotoin and 5-phenylhydantoin. 2-Phenylhydantoic acid was also isolated and was shown to have the (R)(-)-configuration.