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.

In a case involving poisoning with salsalate, a salicylate analogue, the initial blood concentration of the parent drug was underestimated because of the low cross-reactivity of the immunoassay used for the analysis. This resulted in unnecessary additional clinical and laboratory evaluations to find the cause of metabolic acidosis exhibited by the patient. Additional findings led to the conclusion that parent salsalate contributed to patient toxicity. For testing purposes, all salicylate compounds should not necessarily be classified into one salicylic acid category, and there must be detailed communication between the caregiver and the laboratory regarding the specific drug history.