Liquid-chromatographic monitoring of cytosine arabinoside and its metabolite, uracil arabinoside, in serum.
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.
Wermeling
J R
JR
Department of Pathology, University of Cincinnati Hospital, OH 45267.
Pruemer
J M
JM
Hassan
F M
FM
Warner
A
A
Pesce
A J
AJ
D000368:Aged; D001086:Arabinofuranosyluracil / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003561:Cytarabine / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D014529:Uridine / Q000031:analogs & derivatives*
D003561:Cytarabine; D001086:Arabinofuranosyluracil; D014529:Uridine