药学学报, 2022, 57(4): 1123-1129
引用本文:
张思敏, 刘倩, 瞿向阳, 朱建雄, 黄民, 毕惠嫦. 微探针电喷雾串联质谱与液相色谱-电喷雾串联质谱的基质效应对比研究[J]. 药学学报, 2022, 57(4): 1123-1129.
ZHANG Si-min, LIU Qian, QU Xiang-yang, ZHU Jian-xiong, HUANG Min, BI Hui-chang. A comparative study on the matrix effect of micro pen electrospray ionization tandem mass spectrometry and liquid chromatography coupled with electrospray ionization tandem mass spectrometry[J]. Acta Pharmaceutica Sinica, 2022, 57(4): 1123-1129.

微探针电喷雾串联质谱与液相色谱-电喷雾串联质谱的基质效应对比研究
张思敏1, 刘倩1,2, 瞿向阳1, 朱建雄2, 黄民1, 毕惠嫦1,3*
1. 中山大学药学院药物代谢与药动学实验室, 广东 广州 510006;
2. 广东联捷生物科技有限公司, 广东 东莞 523000;
3. 南方医科大学药学院, 广东 广州 510515
摘要:
电喷雾电离(electrospray ionization,ESI)易受基质干扰,影响其定量的准确度、精密度和稳定性。探针电喷雾电离(probe electrospray ionization,PESI)是原位电离的代表之一,无色谱分离,无复杂样品前处理,具有简便、快速、高通量等诸多优点。微探针电喷雾串联质谱(micro pen electrospray ionization tandem mass spectrometry,μPen-ESI-MS/MS)是基于现有的PESI开发的新技术。本文旨在评价μPen-ESI-MS/MS方法用于血浆中药物定量分析的基质效应,并与液相色谱-电喷雾串联质谱(liquid chromatography coupled with electrospray ionization tandem mass spectrometry,LC-ESI-MS/MS)方法的基质效应进行比较。分别建立5种药物血浆样品的μPen-ESI-MS/MS和LC-ESI-MS/MS方法,计算两种方法的基质因子及内标归一化的基质因子。结果表明,他克莫司、氟桂利嗪和地氯雷他定的μPen-ESI-MS/MS方法的离子抑制程度等于或小于初步优化后的LC-ESI-MS/MS方法;5种药物内标归一化的基质因子RSD均小于15%,符合中国药典生物样品定量分析方法验证指导原则的相关要求。综上,本研究考察了所建立的μPen-ESI-MS/MS方法用于血浆中药物定量分析的基质效应,为μPen-ESI-MS/MS新方法用于生物样品定量分析提供实验数据和科学依据。
关键词:    基质效应      探针电喷雾电离      微探针电喷雾串联质谱      液相色谱-电喷雾串联质谱     
A comparative study on the matrix effect of micro pen electrospray ionization tandem mass spectrometry and liquid chromatography coupled with electrospray ionization tandem mass spectrometry
ZHANG Si-min1, LIU Qian1,2, QU Xiang-yang1, ZHU Jian-xiong2, HUANG Min1, BI Hui-chang1,3*
1. Lab of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;
2. Guangdong RangerBio Technologies Co., Ltd., Dongguan 523000, China;
3. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
Abstract:
Electrospray ionization (ESI) is easy to be affected by the biological matrix interferences, and thus the accuracy, precision, and reproducibility of the quantitation are significantly impaired. Probe electrospray ionization (PESI) is one of the most typical ambient ionization, which can ionize molecules without complicated sample preparation at the atmospheric environment, and is superior in simplicity, high efficiency, and high throughput. The micro pen electrospray ionization tandem mass spectrometry (μPen-ESI-MS/MS) method was newly developed based on PESI. In this study, the matrix effect of the μPen-ESI-MS/MS method for drug quantitation in plasma samples was evaluated and compared with the liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method. The μPen-ESI-MS/MS and LC-ESI-MS/MS methods for quantitation of five drugs in rat plasma were established respectively, and the matrix factors (MFs) and internal standard normalised matrix factors (IS normalised MFs) were measured. The results showed that the ion suppression of the μPen-ESI-MS/MS method for tacrolimus, flunarizine, and desloratadine was equal to or less than that of the LC-ESI-MS/MS method; the RSDs of the IS normalised MFs of all five drugs were less than 15%, which met the related requirements of the Pharmacopoeia of the People's Republic of China. Therefore, this study investigated the matrix effect of the μPen-ESI-MS/MS method for quantitative analysis of target drugs in plasma samples and provided new data for the application of μPen-ESI-MS/MS in bioanalysis.
Key words:    matrix effect    pen electrospray ionization    micro pen electrospray ionization tandem mass spectrometry    liquid chromatography coupled with electrospray ionization tandem mass spectrometry   
收稿日期: 2021-11-07
DOI: 10.16438/j.0513-4870.2021-1593
基金项目: 国家自然科学基金资助项目(82025034,81973392);博士后科学基金资助项目(2020M683141).
通讯作者: 毕惠嫦,Tel:86-20-39943470,Fax:86-20-39943000,E-mail:bihchang@mail.sysu.edu.cn
Email: bihchang@mail.sysu.edu.cn
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