Simultaneous determination of six tyrosine kinase inhibitors in human plasma using HPLC-Q-Orbitrap mass spectrometry

Gefitinib, erlotinib, icotinib, crizotinib, lapatinib and apatinib are targeted cancer therapy agents acting through inhibition of tyrosine kinase. Method for quantifying these six drugs in human plasma of patients was required. An HPLC-Q-Orbitrap method (based on HPLC-MS/MS) was developed and valid...

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Veröffentlicht in:Bioanalysis 2017-06, Vol.9 (12), p.925-935
Hauptverfasser: Ni, Mao-Wei, Zhou, Jie, Li, Hui, Chen, Wei, Mou, Han-Zhou, Zheng, Zhi-Guo
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container_end_page 935
container_issue 12
container_start_page 925
container_title Bioanalysis
container_volume 9
creator Ni, Mao-Wei
Zhou, Jie
Li, Hui
Chen, Wei
Mou, Han-Zhou
Zheng, Zhi-Guo
description Gefitinib, erlotinib, icotinib, crizotinib, lapatinib and apatinib are targeted cancer therapy agents acting through inhibition of tyrosine kinase. Method for quantifying these six drugs in human plasma of patients was required. An HPLC-Q-Orbitrap method (based on HPLC-MS/MS) was developed and validated for the simultaneous detection and quantitation of six tyrosine kinase inhibitors in human plasma. Sample was extracted by liquid-liquid extraction (ethyl acetate: tert-Butyl methyl ether, 1:1 v/v). The method shows a high level of accuracy and reproducibility. The lower limit of quantification was 0.02 ng/ml for apatinib, 0.1 ng/ml for crizotinib, 2.0 ng/ml for lapatinib and 0.05 ng/ml for erlotinib, gefitinib and icotinib. This method was successfully used for apatinib monitoring in plasma of patients with NSCLC. This simple and reproducible method has potential for monitoring of tyrosine kinase inhibitors in patients' plasma.
doi_str_mv 10.4155/bio-2017-0031
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subjects Blood Chemical Analysis - methods
Chromatography, High Pressure Liquid - methods
Humans
Limit of Detection
Linear Models
method development
Protein Kinase Inhibitors - blood
Protein Kinase Inhibitors - pharmacology
Protein-Tyrosine Kinases - antagonists & inhibitors
Q-Orbitrap
Tandem Mass Spectrometry - methods
therapeutic drug monitoring
Time Factors
title Simultaneous determination of six tyrosine kinase inhibitors in human plasma using HPLC-Q-Orbitrap mass spectrometry
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