目的 对清胃散基准样品的浓缩干燥工艺进行考察，确定其浓缩干燥工艺，并对清胃散基准样品中关键质量属性（critical quality attributes，CQA）进行研究。方法 通过考察不同浓缩干燥方法，比较样品中异阿魏酸、盐酸小檗碱、盐酸巴马汀及丹皮酚的含量相对于标准煎液的保留率，确定清胃散基准样品的浓缩干燥工艺，结合前期研究出的煎煮工艺，制备15批清胃散基准样品。利用超快速液相色谱-四极杆-飞行时间质谱（ultra fast liquid chromatography-quadrupole time of flight mass spectrometry，UFLC-Q-TOF/MS）分析清胃散基准样品中的化学成分及入血原型成分，结合文献研究初步确定清胃散基准样品CQA。结果 确定了清胃散基准样品的浓缩干燥工艺为原方煎煮液加药液量0.05 g/mL的β-环糊精直接喷雾干燥。分析出清胃散基准样品中化学成分有135个，入血原型成分28个，初步推测决定清胃散基准样品CQA的化学成分有黄连碱、盐酸小檗碱、盐酸巴马汀、表小檗碱、丹皮酚。结论 建立的浓缩干燥工艺在保证最大程度清胃散标准煎液有效成分的基础上适用于现代生产工艺；并且为后续基准样品CQA的确认及制剂开发奠定基础，从而可以更全面地评价清胃散制剂质量的优劣。

Objective To investigate the concentration and drying process of Qingwei San (清胃散) benchmark samples and study its critical quality attributes (CQA).Methods Different concentration and drying methods were performed to compare the retention rates of isoferulic acid, berberine hydrochloride, palmatine hydrochloride and paeonol in the samples relative to the standard decoction, which can determine the concentration and drying process of Qingwei San benchmark samples. A total of 15 batches of benchmark samples were further prepared with the previous processing method. The ultra fast liquid chromatography-quadrupole time of flight mass spectrometry (UFLC-Q-TOF/MS) analysis was performed to analyze the chemical components and blood prototype components in the benchmark sample of Qingwei San, combined with preliminary research to tentatively identify the CQA of Qingwei San benchmark samples. Results The concentration and drying process of the Qingwei San benchmark samples was determined to be direct spray drying with 0.05 g/mL β-cyclodextrin. Moreover, 135 chemical components and 28 prototype components were analyzed in Qingwei San benchmark samples, and coptisine, berberine hydrochloride, palmatine hydrochloride, epiberberine, and paeonol were the potential CQA of Qingwei San benchmark samples. Conclusion The concentration and drying process of Qingwei San standard decoction was established in this study, which may provide a reference for subsequent CQA confirmation of Qingwei San benchmark samples and formulation development, enabling a comprehensive evaluation of the quality of Qingwei San formulations.

R283.6

国家自然科学基金项目资助（81773910）；国家自然科学基金项目资助（82074004）；江苏高校“青蓝工程”项目资助（2020）