基于LC-MS/MS 研究异夏佛塔苷在大鼠体内药代动力学及其绝对生物利用度

建立LC-MS/MS法测定大鼠血浆中异夏佛塔苷的浓度，研究异夏佛塔苷在大鼠体内的药代动力学特性及其绝对生物利用度。分别灌胃给药1.5、3.0、6.0 mg/kg和静脉注射异夏佛塔苷0.5 mg/kg后，建立LC-MS/MS分析方法测定大鼠血浆中异夏佛塔苷的含量，运用 DAS 3.0软件计算药代动力学参数。异夏佛塔苷在1.0~500.0 ng/mL内线性良好(r=0.997 6)，专属性、精密度和准确度、基质效应和提取回收率以及稳定性均符合生物样本分析要求。药代动力学参数显示:灌胃给药低、中、高3个剂量组，c_max分别为(109.34±22.87)、(259.84±95.35)、(499.26±288.09)ng/mL，AUC_0-t分别为(310.57±46.18)、(552.67±207.14)、(1 075.03±371.19)h·ng/mL，t_1/2分别为(2.36±0.22)、(2.91±0.19)、(3.04±0.86)h，t_max分别为(1.03±0.25)、(1.18±0.17)、(1.5±0.43)h，MRT_0-t分别为(11.33±1.53)、(11.27±1.09)、(8.29±0.76)h；静脉注射后，AUC_0-t为(1 536±421.3)h·ng/mL，t_1/2为(2.57±0.46)h，MRT_0-t为(9.55±2.37)h，绝对生物利用度分别为6.73%，5.99%，5.80%。结果表明，本研究所建立的LC-MS/MS分析方法可应用于异夏佛塔苷在大鼠体内的药代动力学特性研究。

Pharmacokinetics and absolute bioavailability of isoschaftoside in rat by LC-MS/MS

The aim of this study was to develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties and absolute bioavailability of isoschaftoside in rats. Blood sampling was performed at different time points after intragastric administration of isoschaftoside(1. 5, 3. 0, 6. 0 mg/kg)and 0. 5 mg/kg by intravenous injection. Isoschaftoside was analyzed by a validated LC-MS/MS method in plasma; the pharmacokinetic parameters and absolute bioavailability were evaluated by software DAS 3. 0. The results showed that the linear concentration ranges of isoschaftoside was 1. 0- 500. 0 ng/mL(r=0. 997 6). The precision, accuracy, matrix effect, sensitivity, dilution reliability and stability met the requirements of biological sample analysis. For ig administration of isoschaftoside(1. 5, 3. 0, 6. 0 mg/kg), the pharmacokinetic parameter c_max was(109. 34±22. 87), (259. 84±95. 35)and(499. 26±288. 09)ng/mL; AUC_0-t was(310. 57±46. 18), (552. 67±207. 14)and(1 075. 03±371. 19)h ·ng/mL; t_1/2 was(2. 36±0. 22), (2. 91±0. 19)and(3. 04±0. 86)h; t_max was(1. 03±0. 25), (1. 18±0. 17)and(1. 5±0. 43)h; MRT_0-t was(11. 33±1. 53), (11. 27±1. 09)and(8. 29±0. 76)h, respectively. For iv administration of isoschaftoside(0. 5 mg/kg), the pharmacokinetic parameter AUC_0-t was(1 536±421. 3)h ·ng/mL; t_1/2 was(2. 57±0. 46)h; MRT_0-t was(9. 55±2. 37)h. Furthermore, the absolute bioavailability was 6. 73%, 5. 99%, 5. 80%, respectively. The LC-MS/MS analysis method established in this study was accurate and sensitive, so it can be applied to the pharmacokinetic study of isoschaftoside.