title: Investigation of the stereoselective in vitro biotransformation of glutethimide by high-performance liquid chromatography and capillary electrophoresis.
abstract: Due to our interest in drugs with a glutarimide structure, we reinvestigated the stereoselectivity of the in vitro biotransformation of the chiral hypnotic-sedative drug glutethimide. Glutethimide enantiomers were separated on a preparative scale by HPLC on cellulose tris(4-methylbenzoate) as chiral stationary phase. The enantiomeric purity was higher than 99%. A reversed-phase HPLC method was developed to determine the metabolites of glutethimide. After incubations with rat liver microsomes both enantiomers formed 5-hydroxyglutethimide as the main metabolite, as well as additional metabolites, of which some were formed stereoselectively. Mass spectrometry of the unknown metabolites indicated a hydroxylation in the ethyl side chain for two of the metabolites. A third metabolite was tentatively identified as desethylglutethimide.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Weinz
authors.forename: G
authors.initials: G
authors.lastname: Blaschke
authors.forename: H M
authors.initials: HM
authors.lastname: Schiebel
mesh_terms: D000818:Animals; D001711:Biotransformation; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D019075:Electrophoresis, Capillary; D005984:Glutethimide / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D006993:Hypnotics and Sedatives; D005984:Glutethimide