19F nuclear magnetic resonance analysis of the carbamate reaction of alpha-fluoro-beta-alanine (FBAL), the major catabolite of fluoropyrimidines. Application to FBAL carbamate determination in body fluids of patients treated with 5'-deoxy-5-fluorouridine.
alpha-Fluoro-beta-alanine (FBAL), the major catabolite of the antineoplastic fluoropyrimidines, is an amino acid which is in equilibrium with its carbamate derivative in weakly alkaline aqueous solutions containing carbonate. In both water and control biological fluids (urine, plasma) spiked with FBAL (and sodium bicarbonate, in some cases), 19F NMR was used: (i) to determine the pH range over which FBAL carbamate is present (pH greater than or equal to 7), the maximum concentration formed occurring around pH 9, (ii) to show that the amino group of FBAL interacts very slowly with a non-protein plasma component to form a compound X, unstable in acid medium. The presumed structure of X is RCONHCH2CHFCOOH, with R different from an alkyl group but still unidentified. The behavior of FBAL in urine and plasma of rats treated with FBAL or 5'-deoxy-5-fluorouridine (5'-dFUrd), a prodrug of 5-fluorouracil, and from patients treated with 5'-dFUrd was investigated. FBAL carbamate was not present in acid medium and was therefore absent in acidic human urine. However, it was found in alkaline rat urine. FBAL carbamate was found in plasma along with the compound X. The 19F NMR spectra of FBAL and derivatives are complex since alpha-fluoro-beta-ureido-propionic acid, the precursor of FBAL in the catabolic pathway of antineoplastic fluoropyrimidines, produces a signal overlapping that of FBAL carbamate, and very close to that of compound X.(ABSTRACT TRUNCATED AT 250 WORDS)
D000409:Alanine / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D001826:Body Fluids / Q000032:analysis; D002219:Carbamates / Q000378:metabolism; D005260:Female; D005467:Floxuridine / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism
D000596:Amino Acids; D002219:Carbamates; D005462:Fluorine Radioisotopes; D005467:Floxuridine; D015091:beta-Alanine; C032348:alpha-fluoro-beta-alanine; D000409:Alanine; C025034:doxifluridine