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

Pharmacokinetics and absolute bioavailability of isoschaftoside in rat by LCMS/MS

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/m L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/m L,AUC0-t分别为(310. 57±46. 18)、(552. 67±207. 14)、(1 075. 03±371. 19) h·ng/m L,t1/2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/m L,t1/2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。

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.