A、丹参酚酸B、人参皂苷Rg1及其在大鼠血浆和脑组织的药代动力学研究> UPLC—MS/MS(1)
[摘要]建立大鼠血漿和脑组织中丹参酮Ⅱa(TSⅡa)、丹酚酸B(SAB)、人参皂苷Rg1(GRg1)的UPLC-MS/MS分析方法，并开展药物动力学研究。选用SD大鼠，单剂量灌胃(ig)复方丹参方，采集血液与脑组织样品，采用UPLC-MS/MS测定血浆和脑组织中TSⅡa、SAB和GRg1的浓度，以Phoenix WinNolin 6.1药动学程序软件对数据进行非房室模型拟合，采用统计矩法计算药动学参数。经方法学考证，3种成分的峰面积与其在血样及脑组织中的浓度线性关系良好(r>0.992 2)；回收率为58.86%～112.1%，日内、日间RSD≤9.7%，准确度及稳定性均符合体内药物分析的要求。大鼠ig给复方丹参方后的血浆药动参数如下：丹参酮Ⅱatmax(1.58±0.081) h，Cmax(725.4±88.20) μg·L-1，AUC0-t(2 101.3±124.85) μg·h·L-1， MRT0-t(3.66±0.05) h；丹酚酸B tmax(1.29±0.21) h，Cmax(307.9±46.75) μg·L-1，AUC0-t(537.4±88.24) μg·h·L-1， MRTlast (2.08±0.11) h；人参皂苷Rg1tmax(1.42±0.20) h，Cmax(460.38±154.60) μg·L-1，AUC0-t(383.4±88.16) μg·h·L-1， MRTlast (1.87±0.046) h。脑组织药动参数如下：丹参酮ⅡA tmax(0.75±0.22) h，Cmax(1.41±0.420) ng·g-1，AUC0-t(4.34±2.48) ng·h·g-1， MRT0-t (4.00±1.90) h；丹酚酸B tmax(1.08±0.20) h，Cmax(21.09±4.850) ng·g-1，AUC0-t(14.83±3.160) ng·h·g-1， MRT0-t(0.99±0.08) h；人参皂苷Rg1tmax(0.50±0.16) h，Cmax(130.96±54.220) ng·g-1，AUC0-t(136.24±34.350) ng·h·g-1， MRT0-t(2.87±0.33) h。该研究所建立的UPLC-MS/MS方法可用于大鼠血浆及脑组织中丹参酮Ⅱa、丹酚酸B、人参皂苷Rg1中的药动学研究。
, 百拇医药
[关键词]UPLC-MS/MS； 丹参酮Ⅱa； 丹酚酸B； 人参皂苷Rg1； 药动学
[Abstract]A sensitive and specific ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of tanshinone Ⅱa(TSⅡa)， salvianolic acid B(SAB) and ginsenoside Rg1(GRg1) in rat plasma and brain tissues. Male healthy Sprague-Dawley(SD) rats were orally given single dose of Fufang Danshen preparation (TS Ⅱa 60 mg·kg-1， SAB 300 mg·kg-1， GRg1 150 mg·kg-1， borneol 300 mg·kg-1)， and their blood samples and brain tissues were collected at different time points. The drug plasma and brain tissue concentrations of the three analytes were determined by UPLC-MS/MS method. Subsequently， the main pharmacokinetics parameters of plasma and brain tissues were calculated by using Phoenix WinNolin 6.1 software. The methodological test showed that all of analytes in both plasma and brain homogenate exhibited a good linearity within the concentration range(r>0.992 2). Their mean recoveries were between 58.86% and 112.1%. Intra-day and inter-day precisions of the investigated components exhibited RSD≤9.7%， and the accuracy(RE) ranged from -9.68% to 8.20% at all quality control levels. The results of accuracy and stability meet the requirements for biopharmaceutical analysis. For TSⅡa， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.58±0.081) h， (725.4±88.20) μg·L-1， (2 101.3±124.85) μg·h·L-1 and (3.66±0.05) h， respectively. For SAB， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.29±0.21) h， (307.9±46.75) μg·L-1， (537.4±88.24) μg·h·L-1 and (2.08±0.11) h， respectively. For GRg1， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.42±0.20) h， (460.38±154.60) μg·L-1， (383.4±88.16) μg·h·L-1 and (1.87±0.046) h， respectively. For TSⅡa， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the brain tissue were (0.75±0.22) h， (1.41±0.42) ng·g-1， (4.34±2.48) ng·h·g-1 and (4.00±1.90) h， respectively. For SAB， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.08±0.20) h， (21.09±4.850) ng·g-1， (14.83±3.160) ng·h·g-1 and (0.99±0.08) h， respectively. For GRg1， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (0.50±0.16) h， (130.96±54.220) ng·g-1， (136.24±34.350) ng·h·g-1 and (2.87±0.33) h， respectively. The developed method was successfully applied in pharmacokinetic studies on content of TS Ⅱa， SAB and GRg1 in rat plasma and brain tissues., 百拇医药(张杰 刘胜兰 王慧 阳国平 李劲平 刘世坤 唐智 裴奇 黄攀豪)
, 百拇医药
[关键词]UPLC-MS/MS； 丹参酮Ⅱa； 丹酚酸B； 人参皂苷Rg1； 药动学
[Abstract]A sensitive and specific ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of tanshinone Ⅱa(TSⅡa)， salvianolic acid B(SAB) and ginsenoside Rg1(GRg1) in rat plasma and brain tissues. Male healthy Sprague-Dawley(SD) rats were orally given single dose of Fufang Danshen preparation (TS Ⅱa 60 mg·kg-1， SAB 300 mg·kg-1， GRg1 150 mg·kg-1， borneol 300 mg·kg-1)， and their blood samples and brain tissues were collected at different time points. The drug plasma and brain tissue concentrations of the three analytes were determined by UPLC-MS/MS method. Subsequently， the main pharmacokinetics parameters of plasma and brain tissues were calculated by using Phoenix WinNolin 6.1 software. The methodological test showed that all of analytes in both plasma and brain homogenate exhibited a good linearity within the concentration range(r>0.992 2). Their mean recoveries were between 58.86% and 112.1%. Intra-day and inter-day precisions of the investigated components exhibited RSD≤9.7%， and the accuracy(RE) ranged from -9.68% to 8.20% at all quality control levels. The results of accuracy and stability meet the requirements for biopharmaceutical analysis. For TSⅡa， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.58±0.081) h， (725.4±88.20) μg·L-1， (2 101.3±124.85) μg·h·L-1 and (3.66±0.05) h， respectively. For SAB， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.29±0.21) h， (307.9±46.75) μg·L-1， (537.4±88.24) μg·h·L-1 and (2.08±0.11) h， respectively. For GRg1， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.42±0.20) h， (460.38±154.60) μg·L-1， (383.4±88.16) μg·h·L-1 and (1.87±0.046) h， respectively. For TSⅡa， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the brain tissue were (0.75±0.22) h， (1.41±0.42) ng·g-1， (4.34±2.48) ng·h·g-1 and (4.00±1.90) h， respectively. For SAB， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (1.08±0.20) h， (21.09±4.850) ng·g-1， (14.83±3.160) ng·h·g-1 and (0.99±0.08) h， respectively. For GRg1， the pharmacokinetics parameters tmax， Cmax， AUC0-t， MRTlast in the plasma were (0.50±0.16) h， (130.96±54.220) ng·g-1， (136.24±34.350) ng·h·g-1 and (2.87±0.33) h， respectively. The developed method was successfully applied in pharmacokinetic studies on content of TS Ⅱa， SAB and GRg1 in rat plasma and brain tissues., 百拇医药(张杰 刘胜兰 王慧 阳国平 李劲平 刘世坤 唐智 裴奇 黄攀豪)