| 引用本文: | 张雨,刘亮峰,郭涛,聂芩,刘岩,许慧鹏,王彩芬,黄文华,张继稳,杨锐,孙立新.基于谱学特征差异研究羟丙基-β-环糊精的多分散取代特征[J].中国现代应用药学,2023,40(10):1297-1306. |
| ZHANG Yu,LIU Liangfeng,GUO Tao,NIE Qin,LIU Yan,XU Huipeng,WANG Caifen,HUANG Wenhua,ZHANG Jiwen,YANG Rui,SUN Lixin.Identification of the differentiation for substitution poly-dispersions of hydroxypropyl-β-cyclodextrins by spectroscopy characteristics[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(10):1297-1306. |
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| 基于谱学特征差异研究羟丙基-β-环糊精的多分散取代特征 |
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张雨1,2, 刘亮峰3, 郭涛2, 聂芩1, 刘岩1, 许慧鹏2, 王彩芬1,2, 黄文华3, 张继稳1,2, 杨锐4, 孙立新1
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1.沈阳药科大学, 辽宁 本溪 117000;2.中国科学院上海药物研究所, 上海 201020;3.丽珠集团利民制药厂, 广东 韶关 512028;4.中国食品药品检定研究院, 国家药品监督管理局药用辅料质量研究与评价重点实验室, 北京 100050
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| 摘要: |
| 目的 研究多取代型羟丙基-β-环糊精(hydroxypropyl-β-cyclodextrins,HP-β-CD)核磁共振氢谱(nuclear magnetic resonance hydrogen spectrum,1H-NMR)、傅里叶变换红外光谱(Fourier transform infrared spectroscopy,FTIR)的谱学特征差异,为建立具有区分力的HP-β-CD质量评价新方法提供依据。方法 选取法国Roquette公司的9批HP-β-CD作为原研品,获得1H-NMR、FTIR谱图,对数据进行预处理后,结合分层聚类分析(hierarchical cluster analysis,HCA)、主成分分析(principal component analysis,PCA)的化学计量学方法,建立HP-β-CD识别模型,研究其分类情况;收集国内3家公司共18批HP-β-CD作为仿制品,同法获得数据并进行处理,与原研品比较,分析其分类归属情况。结果 NMR数据PCA结果显示,9批原研品被分为3类,且与平均取代度没有相关性,同取代度产品间存在明显差异。18批仿制品分为4类,与厂家和取代度也不完全相关,且存在不属于任何一类的离散较远的批次。FTIR数据PCA结果显示,9批原研品被分为了4类,所有样品一起被分为3类,存在离散的批次,每一类均同时包含原研品与仿制品。在2种方法下,HP-β-CD并没有完全按照平均取代度或者厂家的标准分开,说明其取代行为存在多分散性特征,虽然都符合法规要求,但不同批次的内在质量存在差异。结论 基于NMR、FTIR谱学特征的化学计量学分析,对于HP-β-CD的质量评价及仿制品的优化具有重要意义。 |
| 关键词: 羟丙基-β-环糊精 质量评价 多分散性 核磁共振氢谱 傅里叶变换红外光谱 化学计量学 |
| DOI：10.13748/j.cnki.issn1007-7693.20220405 |
| 分类号:R941 |
| 基金项目:国家重点研发计划项目(2020YFE0201700) |
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| Identification of the differentiation for substitution poly-dispersions of hydroxypropyl-β-cyclodextrins by spectroscopy characteristics |
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ZHANG Yu1,2, LIU Liangfeng3, GUO Tao2, NIE Qin1, LIU Yan1, XU Huipeng2, WANG Caifen1,2, HUANG Wenhua3, ZHANG Jiwen1,2, YANG Rui4, SUN Lixin1
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1.Shenyang Pharmaceutical University, Benxi 117000, China;2.Shanghai Institute of Materia, Chinese Academy of Sciences, Shanghai 201020, China;3.Lizhu Group Limin Pharmaceutical Factory, Shaoguan 512028, China;4.National Institute for Food and Drug Control, Key Laboratory of Quality Research and Evaluation of Pharmaceutical Excipients, State Medical Products Administration, Beijing 100050, China
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| Abstract: |
| OBJECTIVE To study the differences of the nuclear magnetic resonance hydrogen spectrum(1H-NMR) and Fourier transform infrared spectroscopy(FTIR) of hydroxypropyl-β-cyclodextrin(HP-β-CD), provide a basis for establishing a new quality evaluation method for HP-β-CD with discriminative power. METHODS Nine batches of HP-β-CD from Roquette were selected as the original products. After preprocessing the data, combined with hierarchical clustering analysis(HCA) and principal component analysis(PCA) stoichiometry methods, the HP-β-CD recognition model was established to study the classification of HP-β-CD. On the other hand, 18 batches of HP-β-CD from 3 domestic companies were collected as imitations and processed similarly. The data were analyzed in comparison with original products, and their species belonging status were observed for quality evaluation. RESULTS PCA results of NMR data showed that 9 batches of original products were divided into 3 categories, and there was no correlation with the average degree of substitution, but there were significant differences between products with the degree of substitution. The 18 batches of imitation products were divided into 4 categories, which were not completely related to the manufacturer and the degree of substitution, and there were distant batches that did not belong to any category. PCA results of FTIR data showed that 9 batches of original research products were divided into 4 categories, and all samples were divided into 3 categories together. There were discrete batches, and each category contained both original research products and imitations. Under the two methods, HP-β-CD was not completely separated according to the average degree of substitution or the manufacturer's standard, indicating that the substitution behavior of HP-β-CD had the characteristics of poly-dispersity. Although they all met the regulatory requirements, there were differences in the intrinsic quality of different batches. CONCLUSION The stoichiometric analysis based on NMR and FTIR spectral characteristics, the analysis of spectroscopy characteristics is of great significance to the quality evaluation of HP-β-CD and the optimization of imitation products. |
| Key words: HP-β-CD quality evaluation substitution behavior 1H-NMR FTIR stoichiometry |
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