A sensitive HPLC-MS/MS method for the simultaneous determination of anemoside B4, anemoside A3 and 23-hydroxybetulinic acid: Application to the pharmacokinetics and liver distribution of Pulsatilla chinensis saponins
A sensitive HPLC-MS/MS method for the simultaneous determination of anemoside B4, anemoside A3 and 23-hydroxybetulinic acid: Application to the pharmacokinetics and liver distribution of Pulsatilla chinensis saponins
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一种同时测定白头翁苷 B4、白头翁苷 A3 和 23-羟基桦木酸的灵敏 HPLC·MS/MS 方法：在白头翁皂苷的药代动力学和肝脏分布中的应用
DOI：
10.1002/bmc.4124
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发表时间：
2018-03-01
影响因子：
1.8
通讯作者：
Huang, Chenggang
中科院分区：
文献类型：
--
作者：
Guo, Xiaozhen;Xie, Yang;Huang, Chenggang
白头翁皂苷是白头翁中的主要活性成分，由于其潜在的乙型肝炎病毒感染和肝癌治疗作用而受到高度关注。本研究建立了灵敏、准确的 HPLC-MS/MS 方法，可同时测定大鼠血浆和肝脏中三种皂苷（白头翁苷 B4、白头翁苷 A3 和 23-羟基桦木酸），并经过充分验证。该方法成功应用于白杨皂苷的药动学和肝脏分布研究。因此，白杨皂苷中含量极低的23-羟基桦木酸在肝脏和肝脏处置前后部位，即门静脉血浆和全身血浆中的暴露量最高，其次是白头翁苷B4，其在白杨皂苷中的含量最高，而白头翁苷A3的暴露量相当有限。 23-羟基桦木酸的肝脏首过效应为71%，白头翁苷B4为27%，白头翁苷A3为37%，与其不同的肝脏分布程度相对应。据我们所知，这是迄今为止首次对黄芪皂苷的肝脏首过效应和分布进行研究。这些结果也为了解白杨皂苷对肝脏疾病的药理作用提供了有价值的信息。
Pulsatilla chinensis saponins, the major active components in the herb, have drawn great attention as potential hepatitis B virus infection and hepatoma treatments. Here, a sensitive and accurate HPLC-MS/MS method was established for simultaneous determination of three saponins - anemoside B4, anemoside A3 and 23-hydroxybetulinic acid - in rat plasma and liver, and fully validated. The method was successfully applied to a pharmacokinetics and liver distribution study of P. chinensis saponins. Consequently, 23-hydroxybetulinic acid, with an extremely low content in the P. chinensis saponins, exhibited the highest exposure in the liver and in sites before and after hepatic disposition, namely, in the portal vein plasma and systemic plasma, followed by anemoside B4, which showed the highest content in the herb, whereas anemoside A3 displayed quite limited exposure. The hepatic first-pass effects were 71% for 23-hydroxybetulinic acid, 27% for anemoside B4 and 37% for anemoside A3, corresponding to their different extents of liver distribution. To our knowledge, this is the first investigation on the liver first-pass effect and distribution of P. chinensis saponins to date. These results also provide valuable information for the understanding of the pharmacological effect of P. chinensis saponins on liver diseases.