Chiral aspects of the human metabolism of ethosuximide

Abstract

Ethosuximide is a chiral drug substance primarily indicated for the treatment of absence seizures. This drug is used clinically as the racemate. The human urinary metabolites of ethosuximide (I) have been studied using chiral gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The metabolites identified were the previously reported unchanged ethosuximide (I) enantiomers, all four stereoisomers of 2-(1-hydroxyethyl)-2-methylsuccinimide (II), and the four stereoisomers of 2-ethyl-3-hydroxy-2-methylsuccinimide (III). Through chemical derivatization methodology and GC/MS (using electron impact ionization [EI] and chemical ionization [CI] techniques) two enantiomers of a previously unreported metabolite of ethosuximide, 2-ethyl-2-hydroxymethylsuccinimide (VI), have been identified.