The development and validation of an LC-MS/MS method for the quantification of CZ112, a prodrug of 9-Nitrocamptothecin in rat plasma

Publication date: Available online 10 November 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Ziming Wang, Changmin Shao, Zhiwei Hu, Jian Zheng, Qiang Zhang, Xiaohan Kou, Zijia Wang, Tao Yu, Zhisong Cao, Yang WangAbstract9-Nitrocamptothecin-20-O-propionate (CZ112) and 9-Nitrocamptothecin (9NC) are the bioactive derivatives of camptothecin (CPT), an alkaloid isolated from Camptotheca acuminata, and have been confirmed to possess high anti-cancer properties. In the present study, 9NC was identified as the major metabolite of CZ112 in rat plasma through HPLC/photodiode array detection (PDA) and liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis. A highly sensitive LC–MS/MS method was developed and validated for the simultaneous analysis of CZ112 and 9NC in rat plasma, and camptothecin-20-O-acetate (CZ44) was used as an internal standard (IS). The calibration curves were linear (r2 > 0.999) over concentrations from 2.5 to 320 ng/mL for both CZ112 and 9NC. The method had an accuracy of 96.7–109.6%, and the intra- and inter-day precision (RSD%) were 10.9% or less for CZ112 and 9NC. The stability data showed no significant degradation occurred under the experimental conditions. This method was successfully applied to the pharmacokinetic study of CZ112 and its metabolite 9NC in rat plasma after intravenous and intragastric administration. The oral bioavailability of CZ112 was 6.2 ± 3.3% (n = 6).Graphical abstract
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research