Isolation and identification of a pyrrolic glutathione conjugate metabolite of the pyrrolizidine alkaloid monocrotaline

Toxicol Lett. 1990 May;51(3):321-9. doi: 10.1016/0378-4274(90)90075-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bile / analysis*
  • Chromatography, High Pressure Liquid
  • Glutathione / isolation & purification*
  • Glutathione / metabolism
  • Liver / metabolism
  • Male
  • Mass Spectrometry
  • Monocrotaline
  • Pyrrolizidine Alkaloids / isolation & purification*
  • Pyrrolizidine Alkaloids / metabolism
  • Rats
  • Rats, Inbred Strains

Substances

  • Pyrrolizidine Alkaloids
  • glutathione-dehydro-retronecine conjugate
  • Monocrotaline
  • Glutathione