School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Center for Certification and Evaluation, Guangdong Food and Drug Administration, Guangdong 510080, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Nov 1;1099:10-17. doi: 10.1016/j.jchromb.2018.09.017. Epub 2018 Sep 14.
Zhishi (ZS) and Zhiqiao (ZQ) are two important traditional Chinese medicines (TCMs) that exert various pharmacological functions due to their active ingredients. However, the oral absorption of these ingredients requires further study. At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay (PAMPA) is one of the most frequently used to predict transcellular passive absorption in in-vitro models. This study aims to establish a new approach to examine an optimal extraction process that can take into account not only the concentration of active ingredients but also the overall absorption properties of the mixtures extracted from TCMs. A high-performance liquid chromatography triple-quadrupole mass spectrometry (HPLC-QqQ-MS/MS) method was validated for the determination of the effective permeability value (P) applied to the above experimental medium. The PAMPA experiment showed that certain active ingredients such as diosmin, rhoifolin, eriocitrin, narirutin, naringin, hesperidin and neohesperidin were not detected in the permeability assay of mono-constituents but were well detected and achieved a better absorption in the permeability assay of the mixture, indicating that certain unknown ingredients may act as cosolvents to improve the solubility or permeability of other ingredients. Furthermore, solid phase extraction (SPE) as an enrichment and purification process enhances absorption. In the present study, a novel in vitro approach was developed to decipher the potential role of TCMs in global absorption, and the extraction process for complex TCMs was described and systematically optimized.
枳实（ZS）和枳壳（ZQ）是两种重要的中药，由于其有效成分，发挥着各种药理作用。然而，这些成分的口服吸收需要进一步研究。在早期药物发现阶段，高通量平行人工膜透过性测定（PAMPA）是最常用来预测细胞间被动吸收的体外模型之一。本研究旨在建立一种新的方法来检查最佳提取过程，不仅要考虑有效成分的浓度，还要考虑从中药中提取的混合物的整体吸收特性。建立了高效液相色谱三重四极杆质谱（HPLC-QqQ-MS/MS）法测定应用于上述实验介质的有效渗透率（P）值。PAMPA 实验表明，某些有效成分，如橙皮苷、柚皮苷、橙皮素、柚皮苷、柚皮苷、橙皮苷和新橙皮苷，在单成分的透过性测定中未被检测到，但在混合物的透过性测定中被很好地检测到并实现了更好的吸收，表明某些未知成分可能作为共溶剂，以提高其他成分的溶解度或透过性。此外，固相萃取（SPE）作为一种富集和纯化过程，增强了吸收。本研究建立了一种新的体外方法来破译中药在整体吸收中的潜在作用，并描述和系统地优化了复杂中药的提取过程。
