Determination of 5-fluorouracil in plasma and liver after oral administration of 5'-deoxy-5-fluorouridine using gas chromatography-mass spectrometry.

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Abstract
A method for determination of 5-fluorouracil (5-FU) has been established for pharmacokinetic study of 5''-deoxy-5-fluorouridine (5''-DFUR), a newly developed prodrug of 5-FU. 5-FU was extracted with diethyl-ether containing 1-propanol and methylated with cH3I in the presence of (CH3)4NOH. The methylated 5-FU was analyzed by gas chromatography-mass spectrometry using 15N2-5-FU as an internal standard. Quantitation was carried out by selected-ion monitoring of molecular ions of N,N-dimethyl-5-FU (m/z 158) and the internal standard (m/z 160). The sensitivity (>2 ng/g sample), specificity and precision of the method were satisfactory for application to clinical studies of this drug. After an oral administration of 5''-DFUR (800 mg/body) to patients with cancer, 5-FU in plasma peaked within 1 h and eliminated with an apparent half life of about 1 h.