The anthracyclines daunorubicin and doxorubicin are cancer chemotherapy agents that complex DNA and are widely utilized clinically. Cumulative cardiotoxicity, however, limits their prolonged use. The novel anthrapyrazole agent, CI-937, which has shown exceptional in vivo anticancer activity and reduced cardiotoxicity in preclinical models has been developed at the Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co. Due to an inability to extract CI-937 reproducibly from biological fluids, high-performance liquid chromatography is not a feasible analytical method. We developed a radioimmunoassay by conjugating CI-937 to porcine thyroglobulin to elicit rabbit antibody which was used with a radioiodinated derivative. The assay was validated for rat plasma using 50 µl of sample with a resulting limit of quantitation of 100 pg/ml. By dilution of samples the assay can quantitate CI-937 levels up to 16 µg/ml. The antiserum is very specific as evidenced by cross-reactivities of less than 0.4% for structural analogues and less than 0.004% for any of the commonly used cancer chemotherapy agents. Analysis of plasma samples from rats treated with a single 5 mg/kg i.v. dose indicated that CI-937 is rapidly cleared from plasma and is extensively bound to tissues.

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