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口服芪苈强心胶囊后大鼠体内 14 种化合物的药代动力学、肝处置和心脏组织分布:超高效液相色谱-串联三重四极杆质谱法。

Pharmacokinetics, hepatic disposition, and heart tissue distribution of 14 compounds in rat after oral administration of Qi-Li-Qiang-Xin capsule via ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry.

机构信息

College of Pharmacy and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, Jinan University, Guangzhou, P. R. China.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, P. R. China.

出版信息

J Sep Sci. 2022 Jul;45(13):2177-2189. doi: 10.1002/jssc.202101008. Epub 2022 May 3.

Abstract

In the present study, a specific and sensitive approach using ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated for the quantitative analysis of 14 constituents in rat plasma, liver, and heart. The method was fully validated and successfully applied to pharmacokinetic, hepatic disposition, and heart tissue distribution studies of 14 compounds after the oral administration of Qi-Li-Qiang-Xin capsule. Ginsenoside Rb1, alisol A, astragaloside IV, and periplocymarin were found to be highly exposed in rat plasma, while toxic components such as hypaconitine, mesaconitine, and periplocin had low circulation levels in vivo. Moreover, sinapine thiocyanate, neoline, formononetin, calycosin, and alisol A exhibited significant liver first-pass effects. Notably, high levels of alisol A, periplocymarin, benzoylmesaconine, and benzoylhypaconine were observed in the heart. Based on high exposure and appropriate pharmacokinetic features in the systemic plasma and heart, astragaloside IV, ginsenoside Rb1, periplocymarin, benzoylmesaconine, benzoylhypaconine, and alisol A can be considered as the main potentially effective components. Ultimately, the results provide relevant information for discovery of effective substances, as well as further anti-heart failure action mechanism investigations of Qi-Li-Qiang-Xin capsule.

摘要

在本研究中,建立并验证了一种使用超高效液相色谱-串联三重四极杆质谱法测定大鼠血浆、肝和心中 14 种成分的定量分析方法。该方法经过充分验证后,成功应用于口服芪苈强心胶囊后 14 种化合物的药代动力学、肝处置和心脏组织分布研究。结果表明,在大鼠血浆中,人参皂苷 Rb1、阿魏酸、黄芪甲苷和杠柳苷是高度暴露的成分,而体内毒性成分如乌头碱、次乌头碱和杠柳毒苷的循环水平较低。此外,芥子酸硫氰酸盐、新诺林、芒柄花素、大豆苷元和阿魏酸表现出明显的肝脏首过效应。值得注意的是,在心脏中检测到阿魏酸、杠柳苷、苯甲酰乌头碱和苯甲酰次乌头碱的含量较高。基于系统血浆和心脏中的高暴露量和适当的药代动力学特征,黄芪甲苷、人参皂苷 Rb1、杠柳苷、苯甲酰乌头碱、苯甲酰次乌头碱和阿魏酸可以被认为是主要的潜在有效成分。最终,研究结果为发现有效物质提供了相关信息,并进一步研究了芪苈强心胶囊的抗心力衰竭作用机制。

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