LAUSR

&NA; A simple and sensitive high performance liquid chromatography with tandem mass spectrometry (LC–MS/MS) method for determination of AZD3759, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in rat plasma and brain homogenate was developed and validated over the range of 1.0–1000 ng/mL. Chromatographic separation was carried out on a C18 column with acetonitrile and 0.1% formic acid in water as mobile phase with gradient elution at a flow rate of 0.4 mL/min. The lower limits of quantification (LLOQs) were 1.0 ng/mL for AZD3759 in both rat plasma and brain homogenate. The intra‐day and inter‐day precision and accuracy of AZD3759 were well within the acceptable limits of variation. The simple and sensitive LC–MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following an oral administration of AZD3759 to rats. HighlightsThe concentration of AZD3759 in rat biomatrices was determined by LC–MS/MS.The pharmacokinetic and brain distribution of AZD3759 in rats were investigated.The results would be useful in further applications of AZD3759.