Mass spectrometric identification and analysis of some aphidicolin metabolites in cancer patients

Biol Mass Spectrom. 1993 Jun;22(6):351-7. doi: 10.1002/bms.1200220607.

Abstract

We used gas chromatography/mass spectrometry to identify and quantitate some aphidicolin metabolites in plasma and urine of patients receiving aphidicolin-17-glycinate. The major metabolite found in plasma was 3-ketoaphidicolin, present at about one thent the concentrations of aphidicolin. 3-Ketoaphidicolin undergoes dehydroxymethylation to give 18-nor-3-ketoaphidicolin. This metabolite was also found in plasma and its concentration reached a maximum of 1% of aphidicolin. Small amounts of aphidicolin and 3-ketoaphidicolin were found free in urine but almost all of the drug was conjugated to glucuronic acid, as shown by mass spectrometric analysis of urine extracts and by enzymatic digestion with beta-glucoronidase followed by gas chromatographic/mass spectrometric analysis.

MeSH terms

  • Animals
  • Aphidicolin / analogs & derivatives
  • Aphidicolin / analysis*
  • Aphidicolin / blood
  • Aphidicolin / urine
  • Gas Chromatography-Mass Spectrometry
  • Glucuronidase
  • Humans
  • Hydrolysis
  • Neoplasms / blood
  • Neoplasms / metabolism*
  • Neoplasms / urine
  • Rats

Substances

  • 18-nor-3-ketoaphidicolin
  • Aphidicolin
  • 3-ketoaphidicolin
  • Glucuronidase