摘要
目的建立液相色谱-串联质谱法测定比格犬血浆中替格瑞洛浓度,并应用于比格犬的药动学研究。方法比格犬血浆样本加甲醇沉淀蛋白后,采用Thermo Hypersil Gold C_(18)(2.1 mm×50 mm,5μm),流动相A为水(0.1%甲酸)、B为甲醇(0.1%甲酸),流速0.50 mL·min^(-1),柱温40℃,进样量5μL。质谱采集方法为ESI负离子及多反应监测(MRM)模式,m/z 521.1/361.1。12只比格犬,分为2组,分别给予替格瑞洛片和市售品,于不同时间点采集血浆,测定血浆中浓度并计算药动学参数。结果该方法选择性好,灵敏度高,替格瑞洛在(2.5~5000)ng·mL^(-1)内线性关系良好,回收率为85.6%~87.9%,批内和批间的准确度(RE%)为-1.7~6.9、精密度(RSD%)为4.5~12.3。比格犬经给予替格瑞洛片和市售品后ρ_(max)和AUC_(0-t),分别为2255.4、2200.4ng·mL^(-1),9624.19547.2ng·h·mL^(-1)。结论本研究方法经过方法学验证,可以准确测定比格犬血浆中替格瑞洛的浓度测定,可以应用于其药动学研究中。替格瑞洛片相对于市售品的相对生物利用度为100.8%。
OBJECTIVE To development a LC-MS/MS method for determination of ticagrelor in dog plasma in vestigate the pharmacokinetics of ticagrelor tablets in Beagle dog.METHODS Dog plasma was precipitated with methanol,the analytes were chromatographed on a Thermo Hypersil Gold C_(18)(2.1 mm×50 mm,5μm)with methanol(0.1%formic acid)and water(0.1%formic acid)as the mobile phase at a flow rate of 0.50 mL·min^(-1).The column temperature was set at 40℃and the injection volume was 5μL.Detection was carried out by the electrospray positive ionization mass spectrometry in the multiple reaction monitoring(MRM)mode,m/z 521.1/361.1.Twelve Beagle dogs were divided into 2 groups,and were adminstrated ticagrelor tablets and reference,and plasma was collected at different time points to determine the concentration in plasma and calculate PK parameters.RESULTS The method exhibited satisfactory selectivity and sensitivity,and ticagrelor exhibited good linearity at the concentration range(2.5-5000)ng·mL^(-1).The extraction recoveries ranged from 85.6%to 87.9%.Intra-and inter-run accuracies(in terms of RE%)and precisions(RSD%)ranged from-1.7 to 6.9 and 4.5 to 12.3,respectively.After oral administration of ticagrelor tablets and reference,the ρ_(max)and AUC_(0-t),in Beagle dogs were 2255.4,2200.4 ng·mL^(-1)and 9624.1、9547.2 ng·h·mL^(-1),respectively.CONCLUSIONS The method is validated and can be used to the determination of ticagrelor in dog plasma and applied to pharmacokinetic studies.Pharmacokinetic results show that the bioavailability of ticagrelor tablets was 100.8%compared with the reference.
作者
刘小雨
蒋婀娜
刘天斌
戚敏
陈凯
LIU Xiao-yu;JIANG E-na;LIU Tian-bin;QI Min;CHEN Kai(Key Laboratory of Biopharmaceuticals,Shandong Academy of Pharmaceutical Sciences,Jinan 250101,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2021年第16期1320-1324,共5页
Chinese Pharmaceutical Journal
关键词
液相色谱-串联质谱法
替格瑞洛片
比格犬血浆
药动学
liquid chromatography tandem mass-spectrometry(LC-MS/MS)
ticagrelor tablets
dog plasma
pharmacokinetics
