Measurement of plasma uracil using gas chromatography-mass spectrometry in normal individuals and in patients receiving inhibitors of dihydropyrimidine dehydrogenase.
A sensitive gas chromatographic-mass spectrometric method is described for reliably measuring endogenous uracil in 100 microl of human plasma. Validation of this assay over a wide concentration range, 0.025 microM to 250 microM (0.0028 microg/ml to 28 microg/ml), allowed for the determination of plasma uracil in patients treated with agents such as eniluracil, an inhibitor of the pyrimidine catabolic enzyme, dihydropyrimidine dehydrogenase. Calibration standards were prepared in human plasma using the stable isotope, [15N2]uracil, to avoid interference from endogenous uracil and 10 microM 5-chlorouracil was added as the internal standard.
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Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20889, USA.
Anderson
L W
LW
Shapiro
J
J
Shapiro
A
A
Grem
J L
JL
Takimoto
C H
CH
D002138:Calibration; D016022:Case-Control Studies; D042943:Dihydrouracil Dehydrogenase (NADP); D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D014498:Uracil / Q000097:blood*
D004791:Enzyme Inhibitors; D014498:Uracil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP)