Analysis of fluorouracil in human plasma by combined gas-liquid chromatography mass spectrometry

Fluorouracil in human plasma of a concentration as low as 2 ng ml-1 can be assayed with the use of gas-liquid chromatography and a multiple ion detector. Fluorouracil is isolated from plasma by anion exchange extraction. The extract is butylated and the derivative obtained extracted into a mixture of cyclohexane + dichloromethane (95:5). An aliquot is submitted to combined gas-liquid chromatography mass spectrometry. The use of chlorouracil or oxygen-18 labelled fluorouracil as internal standard is discussed. Linearity is proven from 100 microgram to 5 ng of fluorouracil per ml plasma. The coefficients of variation are 7.2 and 8.4% for within-run and between-run precision, respectively, at the 50 ng ml-1 level. The biological applicability of our procedure is demonstrated by analysing plasma samples obtained at different time intervals from three patients given 1 g of fluorouracil once intravenously and once orally.