头孢噻肟二聚体脱水物杂质的制备与结构确证  

Preparation and identification of the cefotaxime dimer dehydrated impurity

作　　者：符雅楠 李进[1] 冯芳[2] 尹利辉[1] 姚尚辰[1] FU Ya-nan;LI Jin;FENG Fang;YIN Li-hui;YAO Shang-chen(National Institutes for Food and Drug Control,Beijing 102629,China;China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]中国药科大学,南京211198

出　　处：《中国新药杂志》2022年第19期1943-1951,共9页Chinese Journal of New Drugs

基　　金：中国食品药品检定研究院化药所重点实验室课题项目:抗生素药物杂质分析技术平台的建立与应用(1030050090129)。

摘　　要：目的:制备并确证头孢噻肟二聚体脱水物的化学结构。方法:采用浓溶液降解法得到头孢噻肟钠聚合物浓溶液;采用HPLC法分离纯化头孢噻肟二聚体脱水物杂质;通过冷冻干燥法获得头孢噻肟二聚体脱水物纯品;采用红外光谱(IR)法、紫外光谱(UV)法、质谱分析(MS)法及核磁共振波谱(NMR)法进行测定,与头孢噻肟二聚体进行比较,分析其UV和IR谱图特征吸收峰对应的基团,并对其^(1)H和^(13)C NMR信号进行全归属。结果:通过波谱学的综合解析,首次确证了头孢噻肟二聚体脱水物杂质的聚合位点和立体构型。结论:该研究为头孢菌素类抗生素聚合物杂质的结构研究和致敏性研究提供了技术基础。Objective: To prepare and validate the chemical structure of the cefotaxime dimer dehydrated impurity. Methods: The concentrated polymer solution of cefotaxime sodium was obtained by concentrated solution degradation. The cefotaxime dimer anhydro impurity was separated and purified by preparative HPLC, and the dehydrated impurity was obtained by freeze-drying. The impurity was identified by IR, UV, MS and NMR(including one-dimensional and two-dimensional NMR). The groups corresponding to the characteristic absorption peaks of UV and IR spectra were analyzed, and the ^(1)H and ^(13)C NMR signals were assigned. Results: The polymerization sites and stereoscopic configuration of the dimer anhydro impurity was validated for the first time. Conclusion: This study provided a technical basis for the structural and allergic study of polymer impurities in cephalosporin drugs.

关 键 词：头孢噻肟钠 聚合物杂质 二聚体脱水物 核磁共振波谱法 质谱分析法 紫外光谱法 红外光谱法 

分 类 号：R914[医药卫生—药物化学]