A liquid chromatography-tandem mass spectrometry method for simultaneous quantification of thirty-nine tyrosine kinase inhibitors in human plasma

Authors

Zi-Xuan Guo, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.
Yue-E Wu, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Hai-Yan Shi, Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.
John van den Anker, Division of Clinical Pharmacology, Children's National Hospital, Washington DC, USA; Departments of Pediatrics, Pharmacology & Physiology, Genomics & Precision Medicine, the George Washington University School of Medicine and Health Sciences, Washington DC, USA; Department of Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.
Ping Liang, Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Ying Zheng, Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Xue-Wei Zhao, Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Rui Feng, Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: fengrui-125@163.com.
Wei Zhao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China; NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Shandong University, Jinan, China. Electronic address: zhao4wei2@hotmail.com.

Document Type

Journal Article

Publication Date

11-21-2022

Journal

Journal of pharmaceutical and biomedical analysis

Volume

224

DOI

10.1016/j.jpba.2022.115159

Keywords

LC-MS/MS; Multi-component analysis; Plasma drug concentration; Tyrosine kinase inhibitor

Abstract

Currently, the use of targeted drugs such as tyrosine kinase inhibitors (TKIs) plays an important role in clinical therapy. As the number of approved TKIs continues to increase, existing analysis methods will not be able to meet the growing needs, and will hamper the development of therapeutic drug monitoring (TDM) of TKIs. Based on LC-MS/MS technology, this study tends to develop and validate a multi-component analysis method for simultaneous determination of the concentrations of 39 TKIs in plasma. Spiked plasma was blended with isotope labelled internal standards, and injected into the LC-MS/MS system after protein precipitation by acetonitrile. Chromatographic separation was achieved using an ODS-4 column with gradient elution of formic acid/water (1:1000; v/v) and acetonitrile. Analytes detection was conducted in positive ionisation mode using MRM. The total run time was 8 min. The method validation was conducted by assessing the following parameters: selectivity, linearity and the lower limit of qualification, accuracy and precision, stability, matrix effect and recovery. The concentrations of 39 TKIs showed good linearity within the range of their respective standard curves in plasma, the accuracy of all quality control samples ranged from 85.9% to 114.1%, and the precision was lower than 13.3%. The extraction recovery ranged from 92.6% to 114.7%, and the matrix effect of plasma was lower than 11.3%. This new method was successfully developed, can be used for the determination of drug concentrations in multiple patients with different kinds of TKIs, and will therefore be suitable for TDM of 39 TKIs.

Department

Pediatrics

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