title: Determination of AZD3759 in rat plasma and brain tissue by LC-MS/MS and its application in pharmacokinetic and brain distribution studies.
abstract: 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.
authors.affiliation: Institute of Materia Medica, Shandong Academy of Medical Sciences, Ji'nan 250062, PR China; Key Laboratory for Biotech-Drugs Ministry of Health, Ji'nan 250062, PR China; Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Ji'nan 250062, PR China. Electronic address: mls_xiongs@ujn.edu.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Shandong Yantong Pharmaceutical Technology Co., Ltd., Ji'nan 250014, PR China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Xue
authors.affiliation: Institute of Materia Medica, Shandong Academy of Medical Sciences, Ji'nan 250062, PR China; Key Laboratory for Biotech-Drugs Ministry of Health, Ji'nan 250062, PR China; Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Ji'nan 250062, PR China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Institute of Materia Medica, Shandong Academy of Medical Sciences, Ji'nan 250062, PR China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Institute of Materia Medica, Shandong Academy of Medical Sciences, Ji'nan 250062, PR China.
authors.forename: Peilu
authors.initials: P
authors.lastname: Sun
authors.affiliation: Institute of Materia Medica, Shandong Academy of Medical Sciences, Ji'nan 250062, PR China.
authors.forename: Ruican
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001921:Brain; D002853:Chromatography, Liquid; D010879:Piperazines; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: C000604577:AZD3759; D010879:Piperazines; D011799:Quinazolines
keywords: AZD3759; Brain distribution; Epidermal growth factor receptor tyrosine kinase inhibitor; Pharmacokinetic study; Rat