注射用头孢哌酮钠质量评价

Quality evaluation of cefoperazone sodium for injection

目的对国产与进口注射用头孢哌酮钠的质量现状进行评价。方法采用法定标准检验与探索性研究相结合,对国家药品抽检的66批次样品与调研企业收集的样品进行检验与分析。结果法定标准检验结果显示,66批次注射用头孢哌酮钠合格率为100%。探索性研究揭示,《中国药典》2020版标准的有关物质方法专属性较差,限度较宽,难以保证安全性,建立专属性较强的有关物质方法并可同时控制聚合物杂质;部分企业的样品检出微量的遗传毒性杂质NDMA,建议企业加强对原料生产的监控;国内样品晶体聚结较严重、粒度分布不均匀,复溶时间较长,提示国产原料的结晶工艺仍有提升空间;配伍结果显示部分制剂企业说明书中推荐的配伍稀释液的合理性值得商榷;综合影响因素与加速试验结果,结合各国药典的贮藏条件,表明统一规定该品种在凉暗处或25℃贮藏可能存在一定的风险;包材相容性结果显示覆膜胶塞与中硼硅玻璃瓶更能提升样品的质量。结论目前国产注射用头孢哌酮钠整体质量一般,质量标准有待提高,建议企业优化原料结晶工艺,同时选择质量更好的包材。

Objective This study evaluated the quality condition of domestic and imported cefoperazone sodium for injection.Methods The statutory standard methods combined with exploratory research were used to evaluate the quality of the 66 batches of samples from the national drug market and from pharmaceutical manufacturers.Results The legal test results showed that the qualified rate of 66 batches of cefoperazone sodium for injection was 100%.But exploratory research showed that the specificity of the related substance method of ChP2020 was not good;the limits were broad,so it was difficult to guarantee safety.The related substance method with strong specific properties was established,which could control polymer impurities at the same time.The samples from some pharmaceutical manufacturers detected a trace mount of genetic impurity NDMA.It was suggested that pharmaceutical manufacturers should strengthen the monitoring of raw material production.There were also some problems in domestic samples,such as crystal coalescence;the particle size distribution was not uniform;and the resolution time was long,which all indicated that the crystallization process of domestic raw materials still had much to be improved.The compatibility results showed that the rationality of the compatibility diluents recommended in the instructions of some pharmaceutical manufacturers was questionable.The results of the influence factors and the accelerated test,combined with the storage conditions of pharmacopoeia from various countries,showed that there may be certain risks associated with samples being stored in a cool,dark place at 25℃.The results of package material compatibility showed that the quality of the sample could be improved by the coated rubber plug and the medium-borosilicate glass bottle.Conclusion The quality of domestic cefoperazone sodium for injection at present is normal.The current statutory standard needs to be improved.It is suggested that pharmaceutical manufacturers optimize the crystallization process of raw materials and choose better-quality packaging materials.