Simultaneous and Rapid Determination of Plasma Concentrations of Four Tyrosine Kinase Inhibitors Using Liquid Chromatography/Tandem Mass Spectrometry in Patients with Non–Small Cell Lung Cancer

Abstract

Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor commonly used in Japan. This study aims to develop a simultaneous rapid assay for gefitinib, erlotinib, afatinib, and osimertinib using liquid chromatography-tandem mass spectrometry (LC-MS/MS). These drugs in plasma samples were purified by liquid-liquid extraction with tert-butyl methyl ether, a simple and inexpensive method. The purified drugs were rapidly separated in less than 5 min by isocratic elution using an XBridge Shield RP18 column as the separation column and were sensitively quantified by MS/MS in the electrospray ionization positive mode. The quantification range in plasma for the four drugs was 5–200 nM with a linearity of >0.994 and a lower limit of quantification of 5 nM. The developed method was applied to therapeutic drug monitoring of patients with non–small cell lung cancer treated with oral osimertinib preparation and demonstrated its usefulness.