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

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.