Isolation and identification of a pyrrolic glutathione conjugate metabolite of the pyrrolizidine alkaloid monocrotaline.
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.
Lamé
M W
MW
Department of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.
Morin
D
D
Jones
A D
AD
Segall
H J
HJ
Wilson
D W
DW
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
D011763:Pyrrolizidine Alkaloids; C064161:glutathione-dehydro-retronecine conjugate; D016686:Monocrotaline; D005978:Glutathione