LC-MS/MS method for the determination of an anti-tumor compound C17 in nude mice plasma and its application to a pharmacokinetic study
10.16438/j.0513-4870.2023-0481
- VernacularTitle:LC-MS/MS测定裸鼠血浆中抗肿瘤化合物C17的分析方法及其在药物动力学研究中的应用
- Author:
Qing-yu YAO
1
;
Yao-yao FENG
1
;
Xiao-xue YAN
2
;
Guo-shu CHEN
2
;
Tian-yan ZHOU
1
Author Information
1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Health Science Center, Peking University, Beijing 100191, China
2. School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, China
- Publication Type:Research Article
- Keywords:
LC-MS/MS;
nude mice;
pharmacokinetics;
non-linear mixed effect model
- From:
Acta Pharmaceutica Sinica
2023;58(8):2448-2453
- CountryChina
- Language:Chinese
-
Abstract:
C17 is an orally available anti-tumor compound inhibiting cancer stem cell (CSC). In this study, a stable, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated, and was further applied to a pharmacokinetic study in nude mice receiving C17 by gavage. Using propranolol as the internal standard, the plasma samples were pre-treated by precipitation with methanol and analyzed on an Intersil C8-3 column (100 mm × 2.1 mm, 3 μm), and gradient elution was performed with a mobile phase consisting of 0.1% formic acid aqueous and solution mixed up by 90% isopropanol and 10% acetonitrile. The analyte was detected by a triple quadrupole tandem mass spectrometer, and multiple reaction monitoring was employed to select C17 at m/z 439.3/247.1 and propranolol at m/z 260.2/116.2 in the positive ion mode. The calibration curves were linear (r > 0.995) over the range of 5-800 ng·mL-1. The intra- and inter-day precisions and accuracies were 7.42%-13.22% and -8.99%-8.81% respectively. The method was successfully applied to a PK study in nude mice administered with a single oral dose of 50 mg·kg-1 C17, and the PK data were analyzed with non-linear mixed effect model (NONMEM). Two separated absorption peaks were found in the PK curve of C17, and a two-compartment model with two sequential first-order absorption rate was utilized to describe the PK properties of C17, and the model could provide insights into the physiological process and exposure of C17 in nude mice. All animal experiments were in strict accordance with the regulations of the Biomedical Ethics Committee of Peking University.
