BACKGROUND: The metabolism of fluorouracil and fluorocytosine, two 5-fluoropyrimidine drugs in clinical use, was investigated. METHODS: (19)F nuclear magnetic resonance (NMR) spectroscopy was used as an analytical technique for the detection, identification and quantification of fluorinated metabolites of these drugs in intact human biofluids as well as fluorinated degradation compounds of fluorouracil in commercial vials. RESULTS: (19)F NMR provides a highly specific tool for the detection and absolute quantification, in a single run, of all the fluorinated species, including unexpected substances, present in biofluids of patients treated with fluorouracil or fluorocytosine. Besides the parent drug and the already known fluorinated metabolites, nine new metabolites were identified for the first time with (19)F NMR in human biofluids. Six 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, O(2)-beta-glucuronide of fluorocytosine. CONCLUSION: (19)F NMR studies of biological fluids of patients treated with anticancer fluorouracil or antifungal fluorocytosine have furthered the understanding of their catabolic pathways.
BACKGROUND: The metabolism of fluorouracil and fluorocytosine, two 5-fluoropyrimidine drugs in clinical use, was investigated. METHODS: (19)F nuclear magnetic resonance (NMR) spectroscopy was used as an analytical technique for the detection, identification and quantification of fluorinated metabolites of these drugs in intact human biofluids as well as fluorinated degradation compounds of fluorouracil in commercial vials. RESULTS: (19)F NMR provides a highly specific tool for the detection and absolute quantification, in a single run, of all the fluorinated species, including unexpected substances, present in biofluids of patients treated with fluorouracil or fluorocytosine. Besides the parent drug and the already known fluorinated metabolites, nine new metabolites were identified for the first time with (19)F NMR in human biofluids. Six 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, O(2)-beta-glucuronide of fluorocytosine. CONCLUSION: (19)F NMR studies of biological fluids of patients treated with anticancer fluorouracil or antifungal fluorocytosine have furthered the understanding of their catabolic pathways.
Authors: Kristen E DeMeester; Hai Liang; Matthew R Jensen; Zachary S Jones; Elizabeth A D'Ambrosio; Samuel L Scinto; Junhui Zhou; Catherine L Grimes Journal: J Am Chem Soc Date: 2018-07-23 Impact factor: 15.419
Authors: Alex O Okaru; Tobias S Brunner; Svenja M Ackermann; Thomas Kuballa; Stephan G Walch; Matthias Kohl-Himmelseher; Dirk W Lachenmeier Journal: J Anal Methods Chem Date: 2017-10-18 Impact factor: 2.193