State Key Laboratory of Electroanalytical Chemistry, Jilin Provincial Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, China.
Phytochem Anal. 2021 May;32(3):362-374. doi: 10.1002/pca.2982. Epub 2020 Sep 7.
The formula of Chinese medicine, Ding-Zhi-Xiao-Wan (DZXW), has the distinct feature of compatibility therapy, which is attributed to the interactions of multi-herbs. However, the quantification problem caused by the absence of pure reference standards is a bottleneck to clarify the compatibility advantages from the perspective of pharmacokinetics (PKs).
This study aimed to develop a putative multiple-reaction monitor (PMRM) strategy for exploring the comparative PKs of DZXW and its single herbs.
First, precursor ion and tandem mass spectrometry (MS/MS) chromatograms were obtained via ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight MS (UHPLC-Q-TOF-MS) under different collision energy (CE) values. Then, the two most abundance ions in the MS/MS chromatograms were chosen as product ions, and CE values were selected according to the abundance of the product ion peaks. Next, a PMRM strategy consisting of optimal MRM parameters was constructed. Finally, the established PMRM parameters were imported to UHPLC coupled with triple quadrupole MS (UHPLC-TQ-MS) for quantification.
The strategy was exemplified by the comparative PK study of DZXW and its single herbs. This strategy could extend the PK scopes of multi-components. The quantitative results displayed substantial variations in PK parameters between DZXW and its single herbs.
The PK parameters indicated that the DZXW formula could increase the exposure levels of most ingredients and reduce the maximum concentration (C ) of Radix Polygala, indicating that herb compatibility could produce synergistic effects and diminish possible toxic effects. This study provides a viable orientation for the compatibility investigation of traditional Chinese medicine.
中药方剂定志小丸（DZXW）具有配伍治疗的显著特点，这归因于多味草药的相互作用。然而，由于缺乏纯参考标准，定量问题成为从药代动力学（PKs）角度阐明配伍优势的瓶颈。
本研究旨在开发一种假定的多重反应监测（PMRM）策略，以探索 DZXW 及其单味草药的比较 PKs。
首先，通过超高效液相色谱-四极杆飞行时间质谱（UHPLC-Q-TOF-MS）在不同碰撞能（CE）值下获得前体离子和串联质谱（MS/MS）色谱图。然后，选择 MS/MS 色谱图中最丰富的两个离子作为产物离子，并根据产物离子峰的丰度选择 CE 值。接下来，构建包含最佳 MRM 参数的 PMRM 策略。最后，将建立的 PMRM 参数导入到超高效液相色谱-三重四极杆质谱（UHPLC-TQ-MS）进行定量。
该策略通过 DZXW 及其单味草药的比较 PK 研究进行了举例说明。该策略可以扩展多成分的 PK 范围。定量结果显示 DZXW 及其单味草药之间 PK 参数存在显著差异。
PK 参数表明，DZXW 配方可以提高大多数成分的暴露水平，并降低 Radix Polygala 的最大浓度（C ），表明草药配伍可以产生协同作用，并减少可能的毒副作用。本研究为中药配伍研究提供了可行的方向。
