目的 基于质量标志物（Q-marker）概念，通过筛选脑心通胶囊Q-markers，构建活性化合物-靶点网络，建立脑心通的整体质控方法。方法 采用多元统计方法找到多批次脑心通胶囊的特异性成分，运用基于BATMAN-TCM网络药理学计算平台构建“Q-markers-靶点-通路-疾病”网络，并进行生物学信息注释。进一步建立超高效液相色谱法（UPLC）同时质控Q-markers的分析方法。结果 多元统计分析将桑皮苷A、羟基红花黄色素A、芍药苷、阿魏酸、毛蕊异黄酮苷、迷迭香酸、丹酚酸B、芒柄花素和丹参酮Ⅱ_A 9种成分初步确定为脑心通胶囊整体质控的Q-markers。通过靶点网络构建和拓扑学分析结果推测，Q-markers主要作用于PTGIS、PTGS2、CHRNA10、ENPP1和ADORA2A 5个关键靶点。针对Q-markers建立的UPLC质控方法，线性关系良好（r<0.999），重复性、稳定性、精密度试验RSD均<3%。结论 基于多元统计，网络药理学和UPLC多成分定量测定技术的Q-markers辨析方法，可以初步建立有效成分群多角度的分析方法，并用于脑心通胶囊的质量控制。

Objective This study aimed to establish an integral quality control method for Naoxintong capsules based on the theory of quality markers (Q-marker) in traditional Chinese medicine via multivariable statistical calculation and "active compounds-targets" network construction. Methods Multi-statistical methods were firstly carried out to explore the specific components from different batches of Naoxintong Capsules. The "Q-markers-targets-pathways-diseases" network was constructed using the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) online analysis tool, and biological information annotations were made. Moreover, a simultaneously determination method for Q-markers was established by using ultra-high performance liquid chromatography (UPLC). Results Nine compounds were chose as the Naoxintong Q-markers capsules including mulberroside A, hydroxysafflor yellow A, paeoniflorin, ferulic acid, calycosin-7-glucoside, rosemary acid, salvianolic acid B, formononetin, and tanshinone Ⅱ_A. To verify the prediction, target network construction analysis was performed and indicated that the nine Q-markers mainly targeted five proteins which were PTGIS, PTGS2, CHRNA10, ENPP1, and ADORA2A. Methodological validation showed that the established UPLC method had good linear relationship (r<0.999), and all RSD values were lower than 3% in the repeatability, stability, and precision test. Conclusion Based on the multivariate statistics, network pharmacology analysis, and UPLC multi-component quantitative analysis, a multi-angle analysis method for effective components can be established for the integral quality control of Naoxintong Capsules.

国家中药标准化项目（ZYBZH-C-QIN-45）；国家自然科学基金青年科学基金项目（81501229）；陕西省科技厅“科技新星”培养计划（2017KJXX-71）