波谱学杂志Issue(2)：342-353,12.DOI:10.11938/cjmr20150216
基于NMR指纹谱相关分析的生物类似药高级结构评价
Higher Order Structure Assessment of Biosimilars Based on the Correlation of NMR Spectral Fingerprints
摘要
Abstract
A procedure based on the1H NMR fingerprints of biologics was established for the assessment of higher order structure of biosimilar samples. The global correlation coefficientsr andR2 of binned NMR spectra were used to quantify structural similarity between biosimilars and originators, and a local correlation analysis method was used to find out the specific regions that contribute to the structure differences. This method was applied to the quantitative assessment of daptomycin, a lipopeptide antibiotic with a molecular weight of 1 620, by comparing the higher order structure of the biosimilar active pharmaceutical ingredient (API), its injection and originator injection Cubicin. The results showed that there were significant spectral differences among daptomycin samples, indicating structural differences between daptomycin originator and its biosimilars. Local correlation analysis further revealed the specific spectral regions that contributed to these differences. The method was also applied to a monoclonal antibody drug Trastuzumab, which is a large protein with a molecular weight of 145 423.1H NMR spectra of the originator drug Herceptin and four lots of its biosimilar were recorded and binned for statistical analysis. The correlation coefficientsr andR2 showed that Trastuzumab biosimilars seem to be highly similar to Herceptin. These results demonstrated that the combination of NMR fingerprints and statistical analysis is a powerful and robust technique in biosimilar quality control.关键词
NMR指纹技术/生物类似药/相似度评价/高级结构Key words
NMR fingerprint/biosimilar/similarity assessment/higher order structure分类
数理科学引用本文复制引用
许美凤,方均建,董芳霆,颜贤忠..基于NMR指纹谱相关分析的生物类似药高级结构评价[J].波谱学杂志,2015,(2):342-353,12.基金项目
The National Science and Technology Major Projects (2014ZX09304311-001,2012ZX09301003-001-010) （2014ZX09304311-001,2012ZX09301003-001-010）
