In the present study, a 10-position modified of camptothecin, 10-propionyloxy camptothecin (PCPT) was esterified from 10-hydroxcamptothecin (HCPT), which could metabolize to HCPT in vivo. PCPT displayed a relatively stronger antitumor activity in vitro and in vivo. Thereafter a simple, sensitive and rapid HPLC method coupled with a fluorescence detector was developed and validated for the assay of PCPT and its active metabolite HCPT in rat plasma. The method was validated for accuracy, precision, linearity, selectivity and recovery. The validated method was successfully applied to the pharmacokinetic study of PCPT in rats after intravenous administration. The results showed that PCPT could be mainly converted to HCPT in plasma with the AUC0-∞ value of 3.69 ± 4.44 and 311.16 ± 188.81 ng h/mL for PCPT and HCPT, respectively.
Keywords: 10-hydroxcamptothecin; 10-propionyloxy camptothecin; antitumor activity; pharmacokinetic study.
© 2018 John Wiley & Sons, Ltd.