To quantify the small-molecule kinase inhibitors ceritinib, dacomitinib, lorlatinib, and nintedanib in human plasma by liquid chromatography/triple-quadrupole mass spectrometry

•This UPLC–MS/MS method is the first for the simultaneous analysis of ceritinib, dacomitinib, lorlatinib, and nintedanib in human plasma.•The method was fully validated according to FDA guidelines.•Clinical applicability was demonstrated by quantification of multiple samples from a pharmacokinetic study in patients with lung cancer. Multiple small-molecule kinase inhibitors with specific molecular targets have recently been developed for the treatment of cancer. This article reports the development and validation of an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC–MS/MS) method to simultaneously analyse the small-molecule kinase inhibitors dacomitinib, ceritinib, lorlatinib, and nintedanib in human plasma. For chromatographic analyte separation, an Acquity UPLC® BEH C18 column 1.7 μm, 50 mm x 2.1 mm was used with a binary gradient of pure water/formic acid/ammonium formate (100:0.1:0.02, v/v/v) and methanol/formic acid (100:0.1, v/v). Calibration curves for all small-molecule kinase inhibitors were 5.00–500 ng/mL. Validation of this method met all requirements of the Food and Drug administration. Additionally, clinical applicability was demonstrated by quantification of multiple samples from a pharmacokinetic study in patients with lung cancer.