A liquid chromatography-tandem mass spectrometry method for simultaneous quantification of thirty-nine tyrosine
Zi-Xuan Guo1, Yue-E Wu2, Hai-Yan Shi3
1Department 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.
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.
Insights
A new LC-MS/MS method enables simultaneous measurement of 39 tyrosine kinase inhibitors (TKIs) in plasma, supporting therapeutic drug monitoring (TDM) for personalized cancer treatment.
Area of Science:
- Analytical Chemistry
- Pharmacology
- Clinical Diagnostics
Background:
- Tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy.
- Increasing numbers of approved TKIs necessitate advanced analytical methods.
- Existing methods are insufficient for comprehensive therapeutic drug monitoring (TDM) of TKIs.
Purpose of the Study:
- To develop and validate a multi-component analysis method for 39 TKIs in plasma.
- To establish a robust assay for simultaneous TKI concentration determination.
- To facilitate personalized TDM for a wide range of TKIs.
Main Methods:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed.
- Plasma samples were prepared via protein precipitation with acetonitrile.
- Isotopically labeled internal standards and an ODS-4 column were used for separation and detection.
Main Results:
- The method demonstrated good linearity, accuracy (85.9–114.1%), and precision (<13.3%) for 39 TKIs.
- Extraction recovery ranged from 92.6% to 114.7%, with a matrix effect below 11.3%.
- The total analytical run time was optimized to 8 minutes.
Conclusions:
- A validated LC-MS/MS method for simultaneous determination of 39 TKIs in plasma was successfully developed.
- This method is suitable for therapeutic drug monitoring (TDM) in patients receiving diverse TKIs.
- The assay supports personalized medicine by enabling precise TKI concentration measurements.
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