Abstract：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 C18(2.1 mm×50 mm,5 μm) 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 5 μL. 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 (2.5-5 000) 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 ρmax and AUC0-t in Beagle dogs were 2 255.4、2 200.4 ng·mL-1and 9 624.1、 9 547.2 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.
刘小雨, 蒋婀娜, 刘天斌, 戚敏, 陈凯. 液相色谱-串联质谱法研究比格犬体内替格瑞洛片剂的药动学[J]. 中国药学杂志, 2021, 56(16): 1320-1324.
LIU Xiao-yu, JIANG E-na, LIU Tian-bin, QI Min, CHEN Kai. Pharmacokinetic Study of Ticagrelor Tablets in Beagle Dog by Liquid Chromatography Tandem-Mass Spectrometry. Chinese Pharmaceutical Journal, 2021, 56(16): 1320-1324.
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2021, Vol. 56 
