Determination of AZD3759 in rat plasma and brain tissue by LC–MS/MS and its application in pharmacokinetic and brain distribution studies

•The 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. A simple and sensitive high performance liquid chromatography with tandem mass...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2017-06, Vol.140, p.362-366
Main Authors: Xiong, Shan, Xue, Mingxing, Mu, Yanling, Deng, Zhipeng, Sun, Peilu, Zhou, Ruican
Format: Article
Language:English
Subjects:
Animals
AZD3759
Brain
Brain distribution
Chromatography, Liquid
Epidermal growth factor receptor tyrosine kinase inhibitor
Pharmacokinetic study
Piperazines
Quinazolines
Rat
Rats
Rats, Sprague-Dawley
Reproducibility of Results
Tandem Mass Spectrometry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•The 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. 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 1.0–1000ng/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 0.4mL/min. The lower limits of quantification (LLOQs) were 1.0ng/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.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2017.03.056