School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China; School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
J Chromatogr A. 2018 Jun 1;1552:17-28. doi: 10.1016/j.chroma.2018.03.055. Epub 2018 Mar 28.
High-resolution mass spectrometry (HRMS) provides a powerful tool for the rapid analysis and identification of compounds in herbs. However, the diversity and large differences in the content of the chemical constituents in herbal medicines, especially isomerisms, are a great challenge for mass spectrometry-based structural identification. In the current study, a new strategy for the structural characterization of potential new phthalide compounds was proposed by isomer structure predictions combined with a quantitative structure-retention relationship (QSRR) analysis using phthalide compounds in Chuanxiong as an example. This strategy consists of three steps. First, the structures of phthalide compounds were reasonably predicted on the basis of the structure features and MS/MS fragmentation patterns: (1) the collected raw HRMS data were preliminarily screened by an in-house database; (2) the MS/MS fragmentation patterns of the analogous compounds were summarized; (3) the reported phthalide compounds were identified, and the structures of the isomers were reasonably predicted. Second, the QSRR model was established and verified using representative phthalide compound standards. Finally, the retention times of the predicted isomers were calculated by the QSRR model, and the structures of these peaks were rationally characterized by matching retention times of the detected chromatographic peaks and the predicted isomers. A multiple linear regression QSRR model in which 6 physicochemical variables were screened was built using 23 phthalide standards. The retention times of the phthalide isomers in Chuanxiong were well predicted by the QSRR model combined with reasonable structure predictions (R=0.955). A total of 81 peaks were detected from Chuanxiong and assigned to reasonable structures, and 26 potential new phthalide compounds were structurally characterized. This strategy can improve the identification efficiency and reliability of homologues in complex materials.
高分辨质谱（HRMS）为快速分析和鉴定草药中的化合物提供了有力的工具。然而，草药中化学成分的多样性和含量差异很大，尤其是异构体，这对基于质谱的结构鉴定构成了巨大挑战。在当前的研究中，以川芎中的苯酞类化合物为例，提出了一种新的策略，通过异构体结构预测结合定量结构保留关系（QSRR）分析，用于潜在新苯酞化合物的结构表征。该策略包括三个步骤。首先，基于结构特征和 MS/MS 碎片模式合理预测苯酞化合物的结构：（1）通过内部数据库对收集的原始 HRMS 数据进行初步筛选；（2）总结类似化合物的 MS/MS 碎片模式；（3）鉴定已报道的苯酞化合物，并合理预测异构体的结构。其次，使用代表性的苯酞化合物标准品建立和验证 QSRR 模型。最后，通过 QSRR 模型计算预测异构体的保留时间，并通过匹配检测到的色谱峰和预测异构体的保留时间，合理表征这些峰的结构。使用 23 个苯酞标准品筛选出 6 个物理化学变量，建立了多元线性回归 QSRR 模型。QSRR 模型与合理的结构预测相结合，很好地预测了川芎中苯酞异构体的保留时间（R=0.955）。从川芎中检测到 81 个峰，并分配到合理的结构，鉴定出 26 个潜在的新苯酞化合物。该策略可以提高复杂材料中同系物的鉴定效率和可靠性。
