Gas chromatography-mass spectrometry identification of a novel N3-methylated metabolite of 5'-deoxy-5-fluorouridine in plasma of cancer patients undergoing chemotherapy

J Pharm Biomed Anal. 1996 Aug;14(11):1521-8. doi: 10.1016/0731-7085(96)01798-0.

Abstract

Evidence of in vivo biomethylation of the anticancer pro-drug 5'-deoxy-5-fluorouridine (5'-dFUR) is presented for the first time. Biomethylation seems to occur specifically at the N3 site on the pyrimidine ring. This novel metabolic product was detected by gas chromatography-mass spectrometry of the trimethylsilylated extract of plasma samples from cancer patients undergoing doxifluridine chemotherapy. Considering the observed electron impact fragmentation pattern, the metabolic product was tentatively identified as N3-Me-5'-dFUR. Definite confirmation of the proposed structure was achieved by comparison of the mass spectra and chromatographic characteristics of the suspected metabolite with those of a synthetically prepared reference standard.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / metabolism*
  • Chromatography, High Pressure Liquid
  • Floxuridine / administration & dosage
  • Floxuridine / analogs & derivatives*
  • Floxuridine / blood*
  • Floxuridine / chemical synthesis
  • Floxuridine / chemistry
  • Floxuridine / metabolism*
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Prodrugs / metabolism*
  • Reference Standards

Substances

  • Antineoplastic Agents
  • N(3)-methyl-5'-deoxy-5-fluorouridine
  • Prodrugs
  • Floxuridine
  • doxifluridine