目的 采用超高效液相色譜-飛行時間質譜聯(lián)用（UPLC/Q-TOF-MS）技術、網絡藥理學及蛋白質組學方法，對坤心寧顆粒中的潛在質量標志物（quality markers，Q-Marker）進行預測分析，并建立坤心寧顆粒的質量評價方法。方法 采用UPLC/Q-TOF-MS技術對坤心寧顆粒及給藥后大鼠血漿中的化學成分（入血成分）進行解析；應用蛋白質組學技術挖掘坤心寧顆粒改善腎陰陽兩虛型圍絕經期綜合征（perimenopausal syndrome，PMS）的關鍵信號通路；通過網絡藥理學對入血成分進行靶點預測，聯(lián)合蛋白質組學差異通路分析，確定坤心寧顆粒的潛在Q-Marker；基于HPLC技術建立坤心寧顆粒中8種Q-Marker的定量方法，實現(xiàn)對坤心寧顆粒的質量評價。結果 UPLC/Q-TOF-MS檢測結合質譜數(shù)據(jù)及文獻數(shù)據(jù)分析，鑒定出坤心寧顆粒中20種入血成分，結合網絡藥理學和蛋白質組學技術最終確定梓醇、地黃苷D、芍藥苷、毛蕊異黃酮葡萄糖苷、(−)-丁香樹脂酚-4-O-β-D-呋喃芹糖基-(1→2)-β-D-吡喃葡萄糖苷、仙茅苷、淫羊藿苷和寶藿苷I共8種成分為坤心寧顆粒的Q-Marker；建立HPLC分析方法對15批坤心寧顆粒樣品進行定量測定，結果顯示各批樣品中8種Q-Marker含量均保持穩(wěn)定。結論 借助多維分析技術確定了坤心寧顆粒中的8種潛在Q-Marker，為其全面質量控制提供有效手段。

Objective The potential quality markers (Q-Marker) of Kunxinning Granules (KG, 坤心寧顆粒) were studied by UPLC/Q-TOF-MS technology, network pharmacology and proteomics, and the quality evaluation method of KG was established. Methods UPLC/Q-TOF-MS technology was used to analyze the chemical components of KG and drug-containing plasma. The key signal pathway of KG in improving renal and yin-yang deficiency perimenopausal syndrome (PMS) was explored by proteomics. The potential Q-Marker of KG were determined by network pharmacology and proteomic differential pathway analysis. The quantitative method of eight Q-Marker in KG was established based on HPLC technology to realize the quality evaluation of KG. Results UPLC/Q-TOF-MS detection combined with mass spectrometry data and literature data analysis, identified 20 components in plasma from KG. Combined with network pharmacology and proteomics techniques, a total of eight components, including catalpol, rehmannioside D, paeoniflorin, calycosin-7-O-b-D-glucoside, (−)-syringaresinol-4-O-b-D-apiofuranosyl-(1→2)-b-D-glucopyranoside, curculigoside, icariin and baohuoside I, were identified as the Q-Marker of KG. An HPLC analytical method was established to determine the contents of the eight Q-Marker in 15 batches of KG samples. The results indicated that the contents of the eight Q-Marker in each batch of samples remained stable. Conclusion With the aid of multi-dimensional analysis techniques, eight Q-Marker of KG were determined, providing an effective tool for its comprehensive quality control.

R283.6

中央高?；究蒲袠I(yè)務費專項資金資助（63241465）