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

Fluorouracil in human plasma at 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 flurouracil as internal standard is discussed. Linearity is proven from 100 μg 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.