目的 分析阿胶Asini Corii Colla饮片-中间体-配方颗粒制备过程中的HPLC指纹图谱、指标性成分与能量成分变化，探究其关键质量属性制剂传递规律，建立适宜于阿胶配方颗粒特性的多维质量控制方法。方法 采用茚三酮柱后衍生-氨基酸分析仪建立阿胶饮片、中间体与配方颗粒的HPLC指纹图谱，以对照品进行共有峰指认，并结合化学模式识别分析10批阿胶样品的质量差异；建立同时测定6种氨基酸指标性成分（天冬氨酸、谷氨酸、甘氨酸、丙氨酸、精氨酸、脯氨酸）的定量方法；采用经典方法对蛋白质、脂肪等能量成分进行测定，通过多维度评价阿胶配方颗粒制剂生产各环节，构建动态质控模式。结果 建立了10批阿胶饮片、中间体与配方颗粒的HPLC指纹图谱，共标定21个共有峰，各批次间相似度均≥0.990；阿胶饮片至中间体，主要指标成分氨基酸平均转移率为75.74%～92.09%；中间体至配方颗粒，平均转移率为76.63%～94.84%；阿胶饮片到中间体能量成分平均转移率为96.75%，阿胶中间体到配方颗粒能量成分平均转移率为43.26%。结论 采用茚三酮柱后衍生-氨基酸分析仪构建HPLC指纹图谱、测定多指标性成分，同时对能量成分进行测定，实现对阿胶饮片-中间体-成品的多维度评价，构建阿胶配方颗粒制剂生产全过程动态质控方法，为其后续研发提供参考。

Objective To analyze variations in HPLC fingerprint profiles, characteristic constituents, and energy-related components during the preparation of Ejiɑo (Asini Corii Colla, ACC) decoction pieces, intermediates, and formulated granules. To investigate the transfer patterns of their critical quality attributes. And to establish a multidimensional quality control methodology tailored to the characteristics of ACC formulated granules. Methods HPLC fingerprint chromatograms for ACC decoction pieces, intermediates, and formulated granules were established using an indophenol post-column derivatisation-amino acid analyser method. Common peaks were assigned using reference substances. The quality variations across ten batches of ACC samples were analyzed by combining the fingerprint data with chemometric techniques. Furthermore, a method for the simultaneous quantification of six characteristic amino acids (aspartic acid, glutamate, glycine, alanine, arginine, proline) was developed. Conventional methods were employed to determine energy components, including protein and fat content. The production processes of ACC formulated granules were evaluated multi-dimensionally to construct a dynamic quality monitoring framework. Results Fingerprint chromatograms were established for ten batches of ACC, encompassing its decoction pieces, intermediates, and formulated granules. A total of 21 common peaks were identified, and the similarity among all batches were ≥ 0.990. The average transfer rate of the primary characteristic amino acids was 75.74%—92.09% from the decoction pieces to the intermediates, and 76.63%—94.84% from the intermediates to the formulated granules. The average transfer rate of energy components was 96.75% from the decoction pieces to the intermediates, and the average transfer rate of energy components was 43.26% from the intermediates to the formulated granules. Conclusion The indophenol post-column derivatization‑amino acid analyse method was used to construct HPLC fingerprints, determine multiple characteristic components, and measure energy components simultaneously, realizing a multidimensional evaluation of Ejiao decoction pieces‑intermediates‑finished products. A dynamic quality control method for the whole production process of Ejiao formula granules was established, providing a reference for its further research and development.

R283.6

国家自然科学基金-区域创新发展联合基金重点支持项目（U21A20409）