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目的:建立高效液相色谱-质谱连用(HPLC-MS/MS)测定比格犬血浆中PA-824的浓度,以及进行PA-824在比格犬体内的药动学研究.方法:以卡马西平为内标,生物样品预处理采用乙酸乙酯萃取.色谱柱为Eclipse Plus C18柱(100 mm×2.1 mm,3.5μm),流动相为甲醇-水(90:10),流速为0.6 ml·min-1,柱温为30℃,进样量为5μl,样品分析时间为5 min;电喷雾电离源(ESI),正离子多反应监测扫描分析,PA-824离子对为m/z 360.1→m/z 175.0(碰撞能量:35,解簇电压:65),卡马西平离子对为m/z 237.2→m/z 194.0(碰撞能量:28,解簇电压:83).比格犬口服给药之后,在不同的时间点取血测定血浆中PA-824的含量,然后再用DAS 2.0软件进行药代动力学参数的计算.结果:比格犬口服给药之后,PA-824在50~10000 ng·ml-1(r=0.9991)范围内呈线性关系,回收率为97.7%~105.1%,日内、日间精密度RSD均<5.0%.PA-8243个不同给药量(100,200,500 mg)的AUC0-t分别为(5735.18±1918.76),(11548.47±1838.04),(21987.88±4587.58)ng·min·ml-1,t1/2分别为(14.17±5.97),(11.11±4.39),(13.13±5.46)h,Cmax分别为(626.66±188.48),(2399.13±516.51),(4861.33±2253.61)ng·ml-1.结论:该方法简单、准确、快速、重复性好,适用于比格犬血浆PA-824的药代动力学研究.“,”Objective: To establish a high performance liquid chromatography-tandem mass spectrometric method ( HPLC-MS/MS) method for the determination of PA-824 in the plasma of Beagle dogs, and study the pharmacokinetics of PA-824 in Beagle dogs. Methods:Carbamazepine was used as the internal standard, and the plasma samples were pretreated with ethyl acetate for the liquid-liquid extraction of PA-824. An Eclipse Plus C18 column (100 mm × 2. 1 mm, 3. 5 μm) was used with the mobile phase consisting of methanol-water (90 :10). The flow rate was 0. 6 ml·min-1 and the column temperature was 30 ℃. The injection volume was 5 μl and the sample analysis time was 5 min. The determination was performed with an electrospray ionization ( ESI) source in the positive multiple reaction monitoring (MRM) mode. The ion pairs were m/z 360. 1→m/z 175. 0 (collision energy of 35, solution cluster volt-age of 65) for PA-824 and m/z 237. 2→m/z 194. 0 (collision energy of 28, solution cluster voltage of 83) for carbamazepine. After the oral administration, PA-824 in plasma was measured at different time points, and then the pharmacokinetic parameters were calcu-lated by DAS 2. 0 software. Results: PA-824 showed a good linear relationship within the range of 50-10000 ng · ml-1 ( r =0. 9991). The recovery was 97. 7%-105. 1%, and the RSDs of intra-day and inter-day were less than 5. 0%. At three different dosa-ges (100, 200 and 500 mg) of PA-824, AUC0-twere (5735. 18 ± 1918. 76),(11548. 47 ± 1838. 04) and (21987. 88 ± 4587. 58) ng·min·ml-1,t1/2 were(14.17 ±5.97),(11.11 ±4.39) and (13.13 ±5.46)h,and Cmaxwere(626.66 ±188.48),(2399.13 ± 516.51) and (4861.33 ±2253.61)ng·ml-1, respectively. Conclusion:The method is simple, accurate, rapid and reproducible, and suitable for the pharmacokinetic study of PA-824 in the plasma of Beagle dogs.