title: Isolation and identification of a pyrrolic glutathione conjugate metabolite of the pyrrolizidine alkaloid monocrotaline.
abstract: This report describes the isolation and identification of a monocrotaline-derived, glutathione-conjugated pyrrole obtained from the bile of male Sprague-Dawley rats. Bile obtained from rats given an intravenous bolus of 14C-monocrotaline was fractionated using a series of chromatographic separations. Initial purification with cholestyramine resin removed bile acid and pigment contaminants. Subsequent anion exchange and reversed-phase HPLC separations yielded several fractions that contained the 14C label and tested positive for pyrroles using Ehrlich's reagent. These fractions were analyzed using fast-atom-bombardment tandem mass spectrometry (FAB MS/MS). In addition to glutathione-conjugated dehydroretronecine, at least one other pyrrole present had similar ionic properties. The latter was not present in amounts sufficient for positive identification.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.
authors.forename: M W
authors.initials: MW
authors.lastname: Lamé
authors.forename: D
authors.initials: D
authors.lastname: Morin
authors.forename: A D
authors.initials: AD
authors.lastname: Jones
authors.forename: H J
authors.initials: HJ
authors.lastname: Segall
authors.forename: D W
authors.initials: DW
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001646:Bile / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000302:isolation & purification* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D016686:Monocrotaline; D011763:Pyrrolizidine Alkaloids / Q000302:isolation & purification* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D011763:Pyrrolizidine Alkaloids; C064161:glutathione-dehydro-retronecine conjugate; D016686:Monocrotaline; D005978:Glutathione