Measurement of plasma uracil using gas chromatography–mass spectrometry in normal individuals and in patients receiving inhibitors of dihydropyrimidine dehydrogenase |
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| Authors: | Daoqin Bi Lawrence W. Anderson Jeremy Shapiro Alla Shapiro Jean L. Grem Chris H. Takimoto |
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| Affiliation: | a Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20889, USA;b Laboratory of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, 4 Research Court, Rockville, MD 20850, USA |
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| Abstract: | A sensitive gas chromatographic–mass spectrometric method is described for reliably measuring endogenous uracil in 100 μl of human plasma. Validation of this assay over a wide concentration range, 0.025 μM to 250 μM (0.0028 μg/ml to 28 μg/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 μM 5-chlorouracil was added as the internal standard. |
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| Keywords: | Uracil Eniluracil Dihydropyrimidine dehydrogenase |
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