目的 对比研究桃红四物汤（Taohong Siwu Decoction，TSD）组方药味分别为生品、药典“酒炙”和尊古“酒洗”时的质量差异性，辨识差异标志物。方法 使用Eclipse Plus C₁₈色谱柱（150 mm×3.0 mm，1.8 μm），流动相为乙腈-0.1%磷酸水溶液，进行梯度洗脱，检测波长为230 nm，柱温30 ℃，体积流量0.3 mL/min，进样体积10 μL，建立UPLC指纹图谱。采用中药指纹图谱相似度评价系统确定共有峰，进行相似度评价，运用层次聚类分析（hierarchical cluster analysis，HCA）、主成分分析（principal component analysis，PCA）和偏最小二乘-判别分析（partial least square-discriminant analysis，PLS-DA）对不同组别的TSD进行质量评价，筛选出对TSD整体质量贡献较大的成分，并进行含量测定，评价组方药味不同炮制工艺对TSD质量的影响。结果 选取了20个色谱峰作为指纹图谱共有峰，生品、药典“酒炙”和尊古“酒洗”组内相似度均大于0.996，组间相似度均小于0.980。通过与对照品比对，指认出5-羟甲基糠醛（3号峰）、没食子酸（4号峰）、绿原酸（7号峰）、羟基红花黄色素A（8号峰）、芍药内酯苷（9号峰）、芍药苷（10号峰）、阿魏酸（14号峰）、苯甲酸（17号峰）共8个成分。HCA、PCA和PLS-DA可明显将生品、药典“酒炙”和尊古“酒洗”分为3类，5-羟甲基糠醛、阿魏酸、羟基红黄色素A等成分可能是影响三者质量的差异标志物。含量测定显示，羟基红花黄色素A和阿魏酸在炮制后含量下降，5-羟甲基糠醛在炮制后升高，且相对于药典“酒炙”，尊古“酒洗”后羟基红花黄色素A和阿魏酸含量增加，5-羟甲基糠醛含量降低。结论 TSD组方药味生品、药典“酒炙”以及尊古“酒洗”间存在质量差异，值得深入研究；为经典名方组方药味炮制研究提供依据。

Objective To study the quality difference of Taohong Siwu Decoction (TSD,桃红四物汤) in the original medicinal materials, “stir-fried wine” recorded in Chinese Pharmacopoeia and ancient “wine washing”, and identify the differential markers. Methods The separation was performed on Eclipse Plus C₁₈ column (150 mm×3.0 mm, 1.8 μm), with acetonitrile-0.1% phosphoric acid aqueous solution, detection wavelength 225 nm, column temperature 30 and flow rate 0.3 mL/min for gradient elution, and the UPLC fingerprint was established. The similarity evaluation system of fingerprint of traditional Chinese medicine was used to determine the common peak for similarity evaluation. Hierarchical cluster analysis (HCA), principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) were used to evaluate the quality of TSD in different processing groups, and the components which contributed greatly to the overall quality of TSD were selected and determined. Finally, the content was determined, and the effects of different processing techniques on the quality of TSD were evaluated. Results Twenty chromatographic peaks were selected as the common peaks of the fingerprint. The similarities within the groups were greater than 0.996, and the similarities between the groups were less than 0.980. By comparing with the reference substance, eight components of 5-hydroxymethyl furfural (peak 3), gallic acid (peak 4), chlorogenic acid (peak 7), hydroxysafflor yellow A (peak 8), albiflorin (peak 9), paeoniflorin (peak 10), ferulic acid (peak 14), benzoic acid (peak 17) were identified. HCA, PCA and PLS-DA can clearly divide the original medicinal materials, Pharmacopoeia “stir-fried wine” and respect for antiquity “wine washing” into three categories, and 5-hydroxymethyl furfural, ferulic acid, hydroxysafflor yellow A may be the differential markers affecting the quality of the three processing groups. The content determination showed that the content of hydroxysafflor yellow A and ferulic acid decreased after processing, while 5-hydroxymethylfurfural increased after processing; and compared with Pharmacopoeia “stir-fried wine”, the content of hydroxysafflor yellow A and ferulic acid increased after ancient “wine washing”, while the content of 5-hydroxymethylfurfural decreased. Conclusion There is quality difference between the original medicinal materials, the modern “stir-fried wine” and the ancient “wine washing”, which are worthy of in-depth study. This experiment provides a basis for the research on the processing of classical famous prescriptions.

R283.1;R286.02

国家中医药管理局全国名老中医药专家传承工作室建设项目（国中医药人函[2019]41号）；成都中医药大学“杏林学者”学科人才科研提升计划（CXTD2018003）