基于^(1)H-NMR指纹图谱分区相似度的丹参注射剂质量评价方法  

Quality evaluation method for Danshen Injection based on sectionalized ^(1)H-NMR fingerprint spectral similarity

作　　者：赵芳[1,2,3] 李文竹[1,2] 潘坚扬 杨嘉誉 瞿海斌[1,2] ZHAO Fang;LI Wen-zhu;PAN Jian-yang;YANG Jia-yu;QU Hai-bin(Pharmaceutical Informatics Institute,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;State Key Laboratory of Component-Based Chinese Medicine,Innovation Center in Zhejiang University,Hangzhou 310058,China;Hisun Biopharmaceutical Co.,Ltd.,Hangzhou 311400,China)

机构地区：[1]浙江大学药学院,药物信息学研究所,浙江杭州310058 [2]组分中药国家重点实验室浙江大学交叉创新中心,浙江杭州310058 [3]海正生物制药有限公司,浙江杭州311400

出　　处：《中草药》2022年第17期5312-5320,共9页Chinese Traditional and Herbal Drugs

基　　金：国家“重大新药创制”科技重大专项(2018ZX09201011-002)。

摘　　要：目的 以丹参注射液为研究对象,建立基于^(1)H-NMR指纹图谱分区相似度的质量一致性评价方法。方法 采集81批丹参注射液的^(1)H-NMR光谱,根据代谢物信号的分布规律,将光谱分为氨基酸区、糖类区和酚酸区,分别计算各区光谱的夹角余弦与标准化欧氏距离2种相似度指标,并评价丹参注射液批次质量一致性的性能,并与基于全^(1)H-NMR谱的相似度计算结果进行对比。结果 不同批次丹参注射液间氨基酸、糖类及酚酸的组成均存在一定差异,其中氨基酸、糖类的批间差异较大;同时,欧式距离对成分的批间波动更为敏感。此外,基于全谱的相似度分析结果受糖区特征峰影响极大,对酚酸及氨基酸类成分的批间差异辨识能力较差。结论 基于^(1)H-NMR光谱分区相似度计算法可以更好地辨识不同类别成分的批间波动,较全谱相似度计算法更适用于丹参注射液的一致性评价,为进一步提升中药制剂的质量一致性提供参考。Objective To establish a quality consistency evaluation method for Danshen Injection(丹参注射液)based on the similarity of sectionalized ^(1)H-NMR fingerprint.Methods The ^(1)H-NMR spectra of 81 batches of Danshen Injection were obtained.According to the distribution of various metabolite signals,the spectra were sectionalized into three regions,which were the amino acid region,sugar region,and phenolic acid region,respectively.Then,cosine similarities and standardized Euclidean distances of each region for each spectrum were calculated respectively as the consistency evaluation indexes for Danshen Injection.In addition,the evaluation method results aforementioned was compared with the similarity calculation results based on the full ^(1)H-NMR spectra.Results The results showed that certain fluctuations did exist in the composition of amino acids,carbohydrates,and phenolic acids among different batches of Danshen Injection.Among them,the differences in amino acids and carbohydrates between batches were bigger than those in phenolic acids.At the same time,the Euclidean distance was a more sensitive index to the metabolite fluctuations than cosine similarity.In addition,similarity analysis based on the full ^(1)H-NMR spectrum was significantly affected by the sugar region,and so its ability to distinguish differences in phenolic acids and amino acids was weak.Conclusion Similarities based on sectionalized ^(1)H-NMR spectra can identify the fluctuations of different types of metabolites better.The method proposed in this study is more appropriate for quality control of Danshen Injection than that based on full-spectrum,which will help to provide reference ideas for further improving the quality control level of traditional Chinese medicine preparations。

关 键 词：核磁共振氢谱 丹参注射液 质量控制 质量一致性 相似度分析 氨基酸 糖类 酚酸 丹参素 原儿茶醛 迷迭香酸 紫草酸 丹酚酸B 丹酚酸A 

分 类 号：R283.6[医药卫生—中药学]