Determination of camptothecin analogs in biological matrices by high-performance liquid chromatography

Several analogs of the topoisomerase I inhibitor camptothecin (CPT) have be en introduced in clinical practice in the last decade. All CPT analogs are sensitive to a pH-dependent reversible conversion between a pharmacological ly active lactone form and its inactive, lactone ring-opened, carboxylate f orm, The reversible conversion is also dependent on the, sometimes species- dependent, protein binding properties of the two forms, resulting in differ ent lactone to carboxylate plasma ratios for the various analogs. Pharmacok inetic analysis of the CPT analogs is helpful in understanding the pharmaco dynamic outcome of drug treatment, in clinical as well preclinical studies, Measurement of these analogs is habitually complicated by the chemical ins tability of the lactone moiety and necessitates a rapid centrifugation of t he blood sample, preferably at the bedside of the patient, to collect the p lasma supernatant Since the lactone forms of these drugs are able to diffus e across cell membranes, including those of the red blood cells, rapid coll ection and processing is even necessary in the case where only the total co ncentrations of the CPT analogs are to be measured. Sample pretreatment pro cedures of the CPT analogs topotecan, irinotecan, 9-aminocamptothecin and l urtotecan are summarized and discussed in this review, [(C) 2000 Lippincott Williams & Wilkins.].