Application of micro-pen electrospray ionization tandem mass spectrometry in rapid detection of metabolic stability of testosterone and dextromethorphan
10.16438/j.0513-4870.2021-1650
- VernacularTitle:微探针电喷雾串联质谱方法快速检测睾酮和右美沙芬的代谢稳定性
- Author:
Xiang-yang QU
1
;
Qian LIU
2
;
Si-min ZHANG
3
;
Jian-xiong ZHU
4
;
Min HUANG
3
;
Hui-chang BI
1
Author Information
1. Lab of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
2. Lab of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong RangerBio Technologies Co., Ltd., Dongguan 523000, China
3. Lab of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
4. Guangdong RangerBio Technologies Co., Ltd., Dongguan 523000, China
- Publication Type:Research Article
- Keywords:
ambient ionization mass spectrometry;
probe electrospray ionization;
micro-pen electrospray ionization tandem mass spectrometry;
rug metabolism stability evaluation;
cytochrome P450
- From:
Acta Pharmaceutica Sinica
2022;57(5):1465-1470
- CountryChina
- Language:Chinese
-
Abstract:
Probe electrospray ionization (PESI) is one of the typical types of ambient ionization technology, but its application in quantitative analysis is limited due to its poor sampling stability. Previously, we developed a new micro-pen electrospray ionization tandem mass spectrometry (μPen-ESI-MS/MS) method based on PESI. In this study, a μPen-ESI-MS/MS method to measure testosterone and dextromethorphan in liver microsome samples was developed and validated to further applicate in evaluating drug metabolism stability and CYP450 enzyme activity. A μPen-ESI-MS/MS method for detecting the CYP3A4 substrate testosterone and CYP2D6 substrate dextromethorphan in the liver microsome incubation system were developed, and the linearity, precision and accuracy of the method was validated. The validated method was further used to detect the metabolic stability of testosterone in the liver microsome incubation system. The results showed that the μPen-ESI-MS/MS had high efficiency with 0.3 min spraying time of each sample. The standard curve of the testosterone and dextromethorphan has good linearity (R2 > 0.99), the intra- and inter-batch accuracy of testosterone and dextromethorphan was 95.9%-109.3% and 90.5%-107.3%, respectively; the intra- and inter-batch precision was acceptable with RSD values of 2.4%-13.5% and 3.4%-12.1%. The half-lives of testosterone and dextromethorphan in the liver microsome incubation system were 12 min and 14 min, respectively. This study provided a rapid and sensitive μPen-ESI-MS/MS method for the assay of testosterone and dextromethorphan in liver microsome samples, and provided a new strategy for the evaluation of drug metabolism stability and CYP3A4/CYP2D6 activity.
