Analytical strategy to reveal the in vivo process of multi-component herbal medicine: A pharmacokinetic study of licorice using liquid chromatography coupled with triple quadrupole mass spectrometry
Analytical strategy to reveal the in vivo process of multi-component herbal medicine: A pharmacokinetic study of licorice using liquid chromatography coupled with triple quadrupole mass spectrometry
复制标题
揭示多成分草药体内过程的分析策略：使用液相色谱与三重四极杆质谱联用的甘草药代动力学研究
DOI：
10.1016/j.chroma.2012.08.041
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发表时间：
2012-10-05
影响因子：
4.1
通讯作者：
Guo, De-an
中科院分区：
文献类型：
--
作者：
Qiao, Xue;Ye, Min;Guo, De-an
虽然各种技术已经被用来分析药物代谢物，但多组分草药的代谢很少被完全解决。与化学药物不同，草药中的许多化合物可以进入循环，然后被代谢。此外，这些化合物可能存在代谢相互作用，这使得它们的药代动力学(PK)更加复杂。本工作旨在阐明一种草药的多组分药代动力学，并演示共存成分如何改变PK行为。甘草是一种最常用的中草药，被选为模型。提出了一种比较甘草提取物和9种单一化合物的PK谱的策略。这些化合物是甘草的主要生物活性成分，代表了不同的结构类型(黄酮类、查尔酮类、异黄酮类、皂苷类和香豆素类)。建立了分段选择性反应监测LC/MS/MS方法，同时监测了大鼠血浆中63种甘草代谢物，得到了55种代谢物的PK谱。结果表明，甘草化合物之间的相互作用在4个方面改变了它们的PK行为：苷元的生物利用度提高(甘草素和异甘草素分别增加133倍和109倍)，糖苷的系统循环延长(甘草苷和异甘草苷的Tmax延迟0.3h)，对甘草酸等皂苷的潜在毒性降低，以及II相代谢物的血浆分布发生变化。这是首次系统揭示甘草体内过程的尝试。此外，研究表明，显著的相互作用改变了甘草化合物的药代动力学，这可能是草药的特征。(C)2012爱思唯尔B.V.保留所有权利。
Although various techniques have been employed to analyze drug metabolites, the metabolism of multicomponent herbal medicine has seldom been fully addressed. In contrast to chemical drugs, a number of compounds in herbal medicine could get into circulation and then be metabolized. Moreover, these compounds may have metabolic interactions which make their pharmacokinetics (PK) even more complicated. The present work aims to elucidate the multi-component pharmacokinetics of a herbal medicine, and to demonstrate how PK behaviors were altered by co-existing constituents. Licorice (Glycyrrhiza uralensis Fisch.), a most commonly used herbal medicine, was chosen as a model. A strategy was proposed to compare the PK profiles of licorice extract with those of nine single compounds. These compounds were major bioactive constituents of licorice, and represented various structural types (flavanone, chalcone, isoflavone, saponin, and coumarin). We established a segmented selected reaction monitoring LC/MS/MS method to simultaneously monitor 63 licorice metabolites in rat plasma, and obtained the PK profiles of 55 metabolites. The results indicated that interactions among licorice compounds altered their PK behaviors in 4 aspects: improvement in bioavailability for aglycones (133- and 109-fold increase for liquiritigenin and isoliquiritigenin, respectively), prolongation in system circulation for glycosides (0.3 h delay in T-max for liquiritin apioside and isoliquiritin apioside), decrease of potential toxicity for saponins such as glycyrrhizic acid, and shift in plasma distribution for phase II metabolites. This is the first attempt to systematically reveal the in vivo process of licorice. Moreover, the study indicates noticeable interactions to alter pharmacokinetics among licorice compounds, which may be characteristic for herbal medicines. (C) 2012 Elsevier B.V. All rights reserved.