Urinary metabolites of 2-ethyl-2-methylsuccinimide (ethosuximide) studied by combined gas chromatography mass...

Metabolites of 2-ethyl-2-methylsuccinimide (ethosuximide) have been studied by combined gas chromatography mass spectrometry in a urine sample from a patient treated for petit mal epilepsy with ethosuximide. A new metabolite, 2-carboxymethyl-2-methylsuccinimide, was identified in the urine. It is presumably formed by omega 1-hydroxylation of the ethyl sidechain of the drug followed by a further oxidation of the primary alcohol to a carboxyl group. A previously identified metabolite, 2-ethyl-3-hydroxy-2-methylsuccinimide, was shown in the present study to yield two gas chromatographic peaks (as the N-methylated compound), indicating the existence of a diastereoisomeric pair. Thus, the enzyme responsible for the ring hydroxylation is probably not stereospecific, or alternatively two enzymes with different stereospecificity may exist.