Antitumor drugs possessing topoisomerase I inhibition: applicable separation methods

Separation methods for antitumor drugs capable of topoisomerase I inhibitio n were reviewed in this study. Camptothecin (CPT) its related analogues see med to be promising anticancer drugs that exhibit topoisomerase I inhibitio n. This group of compounds contain a closed alpha -hydroxy-delta -lactone r ing (lactone form) that can undergo reversible hydrolysis to form the open- ring form (carboxylate form). In vitro pharmacological study showed that th e antitumor activity of the lactone form was higher than that of the carbox ylate form. Thus a quantitative method to separate these two forms is impor tant to evaluate the pharmacokinetics and pharmacodynamics of these compoun ds. Nevertheless, current separation methods are complicated by the pH-depe ndent instability of the lactone moiety. High-performance liquid chromatogr aphy (HPLC) coupled with fluorometric detection has been widely used for th e quantitation of the drug as the intact lactone form or as the total lacto ne carboxylate forms in biological matrices. In this report we reviewed cur rent applicable chromatographic techniques for further bioanalytical. studi es of CPT derivatives including sample preparations, HPLC columns, mobile p hases and additives. (C) 2001 Elsevier Science B.V. All rights reserved.