Determination of 5-fluorouracil in plasma by GC/MS using an internal standard. Applications to pharmacokinetics

An analytic method, sensitive to 5 ng/ml and specific, has been set up for the determination of unchanged 5-fluorouracil in human plasma, using gas chromatography--mass spectrometry. Its applications to the pharmacokinetic study of unchanged 5-Fluorouracil in man following an intravenous bolus, 8 hours infusion and oral administration confirmed the non-linearity of the kinetic model. (The clearances obtained with an infusion--from 5 to 60 1/min--are 10 to 60 times higher than the ones observed with a bolus--from 0.5 to 1.4 1/min.) The bioavailability of the oral form seems to be about 60 per cent and the absorption appears to be very fast. A attempt to search a mathematical non-linear model of the 5-Fluorouracil kinetics, using computer simulation, is presented.