The development and validation of an LC-MS/MS method for the quantification of CZ112, a prodrug of 9-Nitrocamptothecin in rat plasma
| Autor: | Xiaohan Kou, Ziming Wang, Tao Yu, Zhiwei Hu, Zijia Wang, Qiang Zhang, Jian Zheng, Yang Wang, Changmin Shao, Zhisong Cao |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Metabolite Clinical Biochemistry Pharmaceutical Science Biological Availability Antineoplastic Agents 01 natural sciences High-performance liquid chromatography Analytical Chemistry chemistry.chemical_compound Pharmacokinetics Liquid chromatography–mass spectrometry Nitrocamptothecin Tandem Mass Spectrometry Drug Discovery medicine Animals Prodrugs Rats Wistar Spectroscopy Chromatography 010405 organic chemistry Chemistry 010401 analytical chemistry Prodrug 0104 chemical sciences Bioavailability Rats Camptothecin medicine.drug Chromatography Liquid |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 179 |
| ISSN: | 1873-264X |
| Popis: | 9-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). |
| Databáze: | OpenAIRE |
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