Flame-ionization GLC assay for fluorouracil in plasma of cancer patients

A rapid and specific flame-ionization GLC method was developed for the determination of plasma fluorouracil. The chloro analog is used as the internal standard. The method involves the isolation of both the drug and the internal standard from plasma on a strong anion-exchange column at pH 10. Elution is performed with acetic acid in methanol. The evaporated eluate is dissolved in tetrahexylammonium hydroxide. An aliquot of the resulting solution is introduced directly into the gas chromatograph, where conversion to the bishexyl derivatives and subsequent separation take place. The extraction recovery from blank plasma, to which fluorouracil was added, was 96.8 +/- 2.4% (SD). Linearity was proven in the range from 0 to 25 micrograms/ml, whereas the detection limit of the method was estimated at about 2 micrograms/ml of plasma. The within-run precision was determined at three different fluorouracil levels. To demonstrate method applicability, plasma samples obtained from cancer patients to whom 1 g of fluorouracil had been administered intravenously were analyzed.