文献类型：期刊文章

作　　者：马元亨[1] 李健[1] 苏清虹[1] 陈文君[1] 卢炜[1,2] 周田彦[1,2]

机构地区：[1]北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室,北京100191 [2]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》

基　　金：National Natural Science Foundation of China(NSFC,Grant No.81473277)

年　　份：2016

卷　　号：25

期　　号：5

起止页码：342-350

语　　种：中文

收录情况：0、CAB、CAS、CSCD、CSCD2015_2016、DOAJ、EMBASE、IC、JST、SCOPUS、ZGKJHX、普通刊

摘　　要：In the present study, a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometric method for the determination of axitinib in nude mouse plasma was developed, validated, and applied to a pharmacokinetic study. Plasma samples were pre-treated by protein precipitation with acetonitrile spiked with erlotinib as an internal standard. The chromatographic separation was accomplished by using a reversed phase C18 column （50 mm×2 mm, 5 μm） with a simple mobile phase system composed of methanol and water （60：40, v/v） at an isocratic flow rate of 0.4 mL/min. The analyte was detected by a triple-quadrupole tandem mass spectrometer via electrospray ionization and multiple reaction monitoring was employed to select both axitinib and erlotinib in the positive ion mode. The calibration curves were linear （r〉0.99） ranging from 1 to 1000 ng/mL, and the lowest level of this range was the lower limit of quantification. The intra- and inter-day precision were 7.7%-12.0%, and the accuracies ranged from 88.6% to 110.4%. This method was successfully applied to a preclinical pharmacokinetic study on female nu/nu nude mice administrated with a single oral dose of axitinib at 120 mg/kg, and the pharmacokinetics was characterized by a one-compartment model with first-order absorption.

关 键 词：AXITINIB LC-MS/MS Nude mice  PHARMACOKINETICS

分 类 号：R965] O657.63[药学类]