Fluorine nuclear magnetic resonance spectroscopy of human biofluids in the field of metabolic studies of anticancer and antifungal fluoropyrimidine drugs.
Fluorine-19 nuclear magnetic resonance (19F NMR) spectroscopy provides a highly specific tool for the detection, identification and quantification of fluorine-containing drugs and their metabolites in biofluids. The value and difficulties encountered in investigations on drug metabolism are first discussed. Then the metabolism of three fluoropyrimidines in clinical use, 5-fluorouracil, 5-fluorocytosine and capecitabine are reported. Besides the parent drug and the already known fluorinated metabolites, 12 new metabolites were identified for the first time with 19F NMR in human biofluids. Nine of them can only be observed with this technique: fluoride ion, N-carboxy-alpha-fluoro-beta-alanine, alpha-fluoro-beta-alanine conjugate with deoxycholic acid, 2-fluoro-3-hydroxypropanoic acid, fluoroacetic acid, O2-beta-glucuronide of fluorocytosine, fluoroacetaldehyde hydrate and its adduct with urea, fluoromalonic acid semi-aldehyde adducts with urea. This emphasizes the high analytical potential of 19F NMR for the furtherance in the understanding of fluoropyrimidine catabolic pathways. 19F NMR should also play a role in the therapeutic monitoring of FU and its prodrugs in specific groups of patients, e.g. hemodialyzed patients or patients with deficiency in FU catabolic enzymes.
Malet-Martino
Myriam
M
Groupe de RMN Biomédicale, Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, Toulouse, France.
Gilard
Véronique
V
Desmoulin
Franck
F
Martino
Robert
R
D000935:Antifungal Agents / Q000378:metabolism / Q000493:pharmacokinetics; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000493:pharmacokinetics; D001826:Body Fluids / Q000737:chemistry / Q000378:metabolism*; D005437:Flucytosine / Q000378:metabolism / Q000493:pharmacokinetics*; D005461:Fluorine / Q000032:analysis; D005472:Fluorouracil / Q000378:metabolism* / Q000493:pharmacokinetics*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*
D000935:Antifungal Agents; D000964:Antimetabolites, Antineoplastic; D005461:Fluorine; D005437:Flucytosine; D005472:Fluorouracil