A UHPLC–MS/MS method for the quantitation of olmutinib in rat plasma

[摘要] Olmutinib (Olita™) is an oral third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) which is used to treat non-small cell lung cancer (NSCLC). A simple, rapid, and sensitive method based on ultra-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) has been developed for the determination of olmutinib. Sample preparation was performed following simple one-step protein precipitation with acetonitrile. Olmutinib and internal standard (dasatinib) were separated on an Eclipse Plus C18 RRHD (2.1 × 50 mm, 1.8 μm) column. The mobile phase consisted of acetonitrile–0.1% formic acid in water with gradient elution. A total run time of 1.7 min was achieved. Detection was performed on a positive-ion electrospray ionization mass spectrometer in multiple reaction monitoring (MRM) mode, using transitions of m/z 487.2 → 402.1 for olmutinib and m/z 488.2 → 401 for dasatinib (IS), respectively. The calibration curve (R2 = 0.999) was linear over the range of 1–500 ng/mL. The recovery of olmutinib ranged from 85.8% to 95.5%. This method can be applied to pharmacokinetic studies of olmutinib.

[学科分类] 化学（综合）

[关键词] Olmutinib;UHPLC–MS/MS;pharmacokinetics;non-small cell lung cancer