F-19 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

  • 1 November 1987
    • journal article
    • research article
    • Vol. 15  (6) , 897-904
Abstract
.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 .gtoreq. 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 as 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, producesa signal overlapping that of FBAL carbamate, and very close to that of compound X. For accurate determination of these different compounds in plasma of patients or rats treated with 5''-dFUrd, the spectra recorded at normal pH should be compared with those at acid pH (pH at which FBAL carbamate and X are transformed into FBAL), or recordings should be carried out using proton decoupling.