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Abstract

Etoposide (VP16 or VP16-213) which was approved by the United States FDA for testicular cancer in 1983, is one of the most effective anticancer agents in the treatment of testicular teratoma, Hodgkin's and non-Hodgkin's lymphomas, small-cell lung cancer, and a variety of other malignancies. Development of bioanalytical methods for VP16 and its metabolites is critical for pharmacokinetic and metabolic studies as well as for mechanisms of action studies. In this review, the current status of the bioanalysis of VP16 and its metabolites are discussed. Recent progress in mechanism of action and metabolism studies is also presented. A number of HPLC methods employing UV, fluorescence, or electrochemical detection are available for the bioanalysis of VP16 and its metabolites. Most of these HPLC methods are sensitive and reliable enough for determining the parent drugs and their metabolites in biological fluids. In addition to radioimmunoassay, enzyme-linked immunosorbent assay (ELISA) for VP16, which is the most sensitive assay method to date, has been developed based on modern immunoassay technology. The primary pharmacological and pharmacokinetic data of GL331, a new derivative of epipodophyllotoxin discovered and developed in author's laboratory, which has shown superior antitumor activity to that of VP16, are also discussed.

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