Isolation of an unknown metabolite of capecitabine,an oral 5-fluorouracil prodrug,and its identification by nuclear magnetic resonance and liquid chromatography-tandem mass spectrometry as a glucuroconjugate of 5'-deoxy-5-fluorocytidine,namely 2'-(beta-D-glucuronic acid)-5'-deoxy-5-fluorocytidine |
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Authors: | Desmoulin Franck Gilard Véronique Martino Robert Malet-Martino Myriam |
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Institution: | Biomedical NMR Group, IMRCP Laboratory, Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse, France. desmouli@chimie.ups-tlse.fr |
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Abstract: | A new metabolite of capecitabine, a prodrug of 5-fluorouracil, was detected by (19)F NMR in bile and liver of rats treated with this anticancer drug. Crude bile and perchloric acid extract of liver was subjected to liquid-liquid separation followed by a pre-purification step on a preparative octadecyl silane column (C(18)). The compound was purified by HPLC optimised to allow the detection of the unknown metabolite and its assumed precursor 5'-deoxy-5-fluorocytidine (5'-DFCR). Treatment with beta-glucuronidase from three sources showed that it was a glucuroconjugate of 5'-DFCR. HPLC-TIS-MS-MS and (1)H NMR allowed identification of the unknown metabolite as 2'-(beta-D-glucuronic acid)-5'-deoxy-5-fluorocytidine. |
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