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Clinical Chemistry 35: 1011-1015, 1989;
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Clinical Chemistry, Vol 35, 1011-1015, Copyright © 1989 by American Association for Clinical Chemistry

Liquid-chromatographic monitoring of cytosine arabinoside and its metabolite, uracil arabinoside, in serum

JR Wermeling, JM Pruemer, FM Hassan, A Warner and AJ Pesce
Department of Pathology, University of Cincinnati Hospital, OH 45267.

This is a "high-performance" liquid-chromatographic method for quantifying the antileukemic drug cytosine arabinoside (cytarabine; 1- beta-D-arabinofuranosylcytosine; Ara-C), with a structural analog, 5- methylcytidine, as the internal standard. We used a C18 reversed-phase column and ammonium acetate (0.5 mol/L, pH 6.5) as the mobile phase, monitoring the column effluent at 280 nm. Tetrahydrouridine was present in the sample-collection tubes to inhibit conversion of cytosine arabinoside to uracil arabinoside. The standard curve is linear to 100 mg/L. Analytical recovery is 98%. Coefficients of variation for within- run and between-run imprecision were 2.0% and 4.3% at 20 mg/L and 2.7% and 2.7% at 80 mg/L, respectively. Assay sensitivity was limited by the amount of endogenous material in each patient's serum, making assay of a pre-infusion sample necessary for accurate calculations. In a trial patient population, the assay was shown to have potential for the detection of toxic concentrations in patients receiving high doses of Ara-C.




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Copyright © 1989 by the American Association for Clinical Chemistry.