Abstract |
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 microliters 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 micrograms/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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Authors | G D Nordblom, L A Pachla, T Chang, L R Whitfield, H D Showalter |
Journal | Cancer research
(Cancer Res)
Vol. 49
Issue 19
Pg. 5345-51
(Oct 01 1989)
ISSN: 0008-5472 [Print] United States |
PMID | 2766301
(Publication Type: Journal Article)
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Chemical References |
- Anthraquinones
- Antineoplastic Agents
- Pyrazoles
- teloxantrone
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Topics |
- Animals
- Anthraquinones
(analysis, blood, pharmacokinetics)
- Antibody Specificity
- Antineoplastic Agents
(analysis, blood)
- Chemical Phenomena
- Chemistry
- Cross Reactions
- Female
- Male
- Pyrazoles
(analysis, blood, pharmacokinetics)
- Rabbits
- Radioimmunoassay
(methods)
- Rats
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