【摘要】 目的:建立测定比格犬血浆中特拉唑嗪的液相色谱-串联质谱法,研究该药不同剂型的药物动力学特点。方法:取血浆样品0.2 mL经液-液萃取后,以甲醇-水-甲酸(70:30:0.5)为流动相,用Diamonsil C18柱分离,采用大气压化学离子源三重四极杆串联质谱,以选择反应监测(SRM)方式进行检测。用于定量分析的离子反应分别为m/z 388→290(特拉唑嗪)和m/z256→167(内标,苯海拉明)。结果:特拉唑嗪线性范围为0.2～100.0 ng·mL-1,定量下限为0.2 ng·mL-1,日内、日间精密度(RSD)均小于6.0%,准确度(RE)在±6.4%以内。应用此法研究比较了6只比格犬单剂量口服盐酸特拉唑嗪缓释片及普通片2 mg后的药物动力学特点,测得缓释片与普通片的主要药动学参数如下:Tmax(h)分别为4.2±1.0和2.0±1.1,Cmax(ng·mL-1)分别为44.6±8.1和59.3±13.1,T1/2(h)分别为9.4±1.9和11.0±1.5,AUC0-t(ng·h·mL-1)分别为624.7±144.1和674.8±194.2。盐酸特拉唑嗪缓释片的Tmax明显大于普通片,而Cmax略小,表明该受试制剂具有缓释特征。结论:首次报道了研究特拉唑嗪犬体内药物动力学特点的方法,该法专属、灵敏、快速,适用于特拉唑嗪制剂的生物等效性研究。更多还原

【Abstract】 Objectives: To establish a LC/MS/MS method for determination of terazosin in Beagle dogs plasma and to study its pharmacokinetics. Methods: Terazosin and internal standard diphenhydramine were extracted from plasma with liquid -liquid extraction,then separated on a Diamonsil C18 column. The mobile phase consisted of metha-nol - water - formic acid (70: 30: 0. 5 ). Atmospheric pressure chemical ionization source was applied and operated in positive ion mode. Selected reaction monitoring( SRM) mode with the transitions of m/z 388→290 and m/z 256→167 was used to quantify terazosin and internal standard,respectively. Results:The linear calibration curve was obtained in the concentration range of 0. 2 - 100. 0 ng·mL-1. The lower limit of quantification was 0. 2 ng· mL -1. The inter - and intra-day precision (RSD) was below 6. 0% , and the accuracy (RE) was within ±6.4% calculated from QC samples. The method was used to determine the concentration of terazosin in plasma after a single 2 mg dose of terazosin sustained release and ordinary tablets were administered to six Beagle dogs. The pharmacokinetic parameters of terazosin in dogs were reported: Tmax (h) were 4. 2±1. 0 and 2. 0 ±1. 1, Cmax ( ng·mL -1 ) were 44. 6±8.1 and 59. 3±13. 1,T1/2(h)were 9. 4 ± 1. 9 and 11. 0 ±1. 5,AUC0-t(ng · h · mL-1)were 624. 7±144. 1 and 674. 8±194. 2,for sustained released and ordinary tablets respectively. The test formulation showed longer Tmax and lower Cmax than ordinary tablets, implying that the test formulation possessed sustained release property. Conclusions: The method was proved to be robust, convenient, and suitable for pharmacokinetic study of terazosin in dogs.更多还原