摘要
目的 对国内市场中不同企业的注射用亚胺培南西司他丁钠的质量状况进行评价,发现质量风险点,为仿制药一致性评价提供质量控制关键点。方法 采用法定检验结合探索性研究的方法对样品进行检验,统计分析注射用亚胺培南西司他丁钠的整体质量水平,分析不同企业产品的差异。结果 按法定标准检验,80批次抽验样品结果均符合规定。但发现原研产品的复溶时间更快;不同企业的产品有关物质和含量结果差异较大;现行质量标准差异较大亟待提高统一。探索性研究表明,样品复溶时间与制剂中亚胺培南晶癖及粒度相关;采用LC/MS等方法对本品有关物质的来源进行了归属,对部分杂质结构进行了推断;对本品的含量测定方法进行了优化。结论 国内市场中注射用亚胺培南西司他丁钠的质量总体较好;在开展仿制药一致性评价工作中,需关注亚胺培南的晶癖以及制剂的有关物质、含量、充氮工艺和异亚丙基丙酮等质量关键点;现行标准有待统一和提高。
Objective This study evaluated the quality status of imipenem and cilastatin sodium for injection from different manufacturers in the domestic market,found out the quality risk points,and provided key quality control points for the consistency evaluation of generic drugs.Methods The statutory testing methods combined with the exploratory research were used to examine samples,and the quality status of imipenem and cilastatin sodium for injection and the differences between different manufacturers were also analyzed.Results According to the statutory testing of 80 baths,all complied with regulations.However,it was found that the original products were dissolved faster.There were significant differences in related substances and assays from the productions of different manufacturers.And there were significant differences in current standards;therefore,the statutory standards needed to be improved and unified.It was shown that the solubility of the sample was related to the crystal habit and granularity of imipenem by exploratory research.The source and the structure of some impurities were identified by LC/MS.The determination method of the assay was optimized.Conclusion The quality of imipenem and cilastatin sodium for injection in the domestic market was good;in conducting consistency evaluations of generic drugs,the crystal habit of imipenem,related substances,contents,nitrogen charging technology and mesityl oxide for the injection should be paid attention to.The statutory standards needed to be integrated and improved.
作者
彭洁
贾艳花
李佩
肖慧
罗嘉琳
李何杏
王婷婷
洪建文
Peng Jie;Jia Yanhua;Li Pei;Xiao Hui;Luo Jialin;Li Hexing;Wang Tingting;Hong Jianwen(Guangdong Institute for Drug Control,Guangzhou 510663)
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2024年第3期297-303,共7页
Chinese Journal of Antibiotics
基金
广东省药品监督管理局科技创新项目(No.2022TDZ05和No.2023TDZ02)。
关键词
注射用亚胺培南西司他丁钠
质量分析
晶癖
有关物质
含量
Imipenem and cilastatin sodium for injection
Quality analysis
Crystal habit
Related substances
Contents
