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通过毛细管电泳-串联质谱联用及在线堆积预富集法测定酪氨酸激酶抑制剂

Determination of Tyrosine Kinase Inhibitors via Capillary Electrophoresis with Tandem Mass Spectrometry and Online Stacking Preconcentration.

作者信息

Petr Jan

机构信息

Department of Analytical Chemistry, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, 77146 Olomouc, Czech Republic.

出版信息

Pharmaceuticals (Basel). 2023 Jan 25;16(2):186. doi: 10.3390/ph16020186.

Abstract

Capillary electrophoresis connected with tandem mass spectrometry was employed for the development of a method for determination of various tyrosine kinase inhibitors in plasma samples. A stacking online preconcentration with a 120 cm-long capillary was used for the determination of bosutinib, dasatinib, canertinib, and erlotinib at physiologically relevant concentrations. The optimization included both capillary electrophoresis and mass spectrometry steps. Under optimal conditions, 50 mM formic acid pH 2.5, an injection time of 120 s, and an optimized mass spectrometry set-up (as sheath liquid composition 75:24.9:0.1 (/) methanol, water, formic acid, and appropriate conditions for ion transitions), LODs in a range of 3.9-23.0 nmol·L were observed. The method was validated in terms of linearity, limit of detection, limit of quantification, repeatability of migration times and peak area, and recovery using plasma as a matrix for analytes. The results showed that this method has great promise for use in many analytical tasks, e.g., therapeutic drug monitoring.

摘要

采用毛细管电泳-串联质谱联用技术开发了一种测定血浆样品中多种酪氨酸激酶抑制剂的方法。使用一根120厘米长的毛细管进行堆积在线预富集,用于测定生理相关浓度下的博舒替尼、达沙替尼、卡奈替尼和厄洛替尼。优化过程包括毛细管电泳和质谱步骤。在最佳条件下,即50 mM pH 2.5的甲酸、120秒的进样时间以及优化的质谱设置(鞘液组成75:24.9:0.1(/)甲醇、水、甲酸以及离子跃迁的合适条件)下,检测限在3.9 - 23.0 nmol·L范围内。该方法在以血浆为分析物基质的线性、检测限、定量限、迁移时间和峰面积的重复性以及回收率方面进行了验证。结果表明,该方法在许多分析任务中,如治疗药物监测,具有很大的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72da/9962873/13ba2d327796/pharmaceuticals-16-00186-g001.jpg

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