Metabolism of 14C-busulfan in isolated perfused rat liver

Eur J Drug Metab Pharmacokinet. Jan-Mar 1987;12(1):71-6. doi: 10.1007/BF03189864.

Abstract

1,4-14C Busulfan gave one main metabolite in the isolated perfused rat liver during 4 hr cyclic perfusion. The cumulative bile excretion contained about 38% of the total radioactivity. About 1% of unchanged 14C-busulfan was excreted in the bile. The metabolite was identified as gamma-glutamyl-beta-(S-tetrahydrothiophenium) alanyl-glycine (sulfonium ion of glutathione) by 252Cf-plasma desorption time-of-flight mass spectrometry. The formation of the metabolite was drastically decreased when the glutathione-S-transferase was inhibited, which indicates that the major reaction of busulfan with glutathione is enzymatic in nature. The sulfonium ion was more stable in the perfusate (t1/2 = 22.4 hr, 37 degrees C) than in the bile (t1/2 = 3.2 hr, 37 degrees C) at pH 7.4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism
  • Busulfan / metabolism*
  • Chromatography, High Pressure Liquid
  • Drug Stability
  • Glutathione Transferase / metabolism
  • In Vitro Techniques
  • Liver / metabolism*
  • Male
  • Mass Spectrometry
  • Perfusion
  • Rats
  • Rats, Inbred Strains

Substances

  • Glutathione Transferase
  • Busulfan