目的 采用超高效液相色譜-飛行時(shí)間質(zhì)譜聯(lián)用（UPLC/Q-TOF-MS）技術(shù)、網(wǎng)絡(luò)藥理學(xué)及蛋白質(zhì)組學(xué)方法，對(duì)坤心寧顆粒中的潛在質(zhì)量標(biāo)志物（quality markers，Q-Marker）進(jìn)行預(yù)測(cè)分析，并建立坤心寧顆粒的質(zhì)量評(píng)價(jià)方法。方法 采用UPLC/Q-TOF-MS技術(shù)對(duì)坤心寧顆粒及給藥后大鼠血漿中的化學(xué)成分（入血成分）進(jìn)行解析；應(yīng)用蛋白質(zhì)組學(xué)技術(shù)挖掘坤心寧顆粒改善腎陰陽(yáng)兩虛型圍絕經(jīng)期綜合征（perimenopausal syndrome，PMS）的關(guān)鍵信號(hào)通路；通過(guò)網(wǎng)絡(luò)藥理學(xué)對(duì)入血成分進(jìn)行靶點(diǎn)預(yù)測(cè)，聯(lián)合蛋白質(zhì)組學(xué)差異通路分析，確定坤心寧顆粒的潛在Q-Marker；基于HPLC技術(shù)建立坤心寧顆粒中8種Q-Marker的定量方法，實(shí)現(xiàn)對(duì)坤心寧顆粒的質(zhì)量評(píng)價(jià)。結(jié)果 UPLC/Q-TOF-MS檢測(cè)結(jié)合質(zhì)譜數(shù)據(jù)及文獻(xiàn)數(shù)據(jù)分析，鑒定出坤心寧顆粒中20種入血成分，結(jié)合網(wǎng)絡(luò)藥理學(xué)和蛋白質(zhì)組學(xué)技術(shù)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(shù)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(duì)15批坤心寧顆粒樣品進(jìn)行定量測(cè)定，結(jié)果顯示各批樣品中8種Q-Marker含量均保持穩(wěn)定。結(jié)論 借助多維分析技術(shù)確定了坤心寧顆粒中的8種潛在Q-Marker，為其全面質(zhì)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(wù)費(fèi)專(zhuān)項(xiàng)資金資助（63241465）