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 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.