国产注射用头孢噻吩钠质量研究与分析  

Quality evaluation and analysis of domestic cefalotin sodium for injection

作　　者：杨美成[1,2] 秦峰[2] 刘浩[2] 闻宏亮[2] 裘亚[2] 赵敬丹[2] 张文[1] 

机构地区：[1]华东师范大学,上海200065 [2]上海市食品药品检验所,上海201203

出　　处：《药物分析杂志》2014年第8期1449-1456,共8页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:研究国产注射用头孢噻吩钠的质量,分析质量标准中需要完善的指标。方法:按照2013年度国家药品评价性抽验计划总体要求,采用现行标准对46批抽验样品进行法定检验,建立并完善了用于探索性研究的有关物质、金属杂质、残留溶剂检测等多个方法。结果:法定检验结果显示46批注射用头孢噻吩钠合格率为100%。探索性研究发现各国药典方法对杂质A的认定有误,并首次建立了头孢噻吩3-位置异构体的定量方法。根据斑马鱼胚胎急性毒性试验和小鼠急性毒性试验的结果,杂质相对毒性大小为:头孢噻吩3-位置异构体>杂质A>杂质B>头孢噻吩。采用电感耦合等离子体发射光谱仪(ICPOES)和电感耦合等离子体质谱(ICP-MS)对可能存在的金属杂质进行筛选,发现均可检出锌且含量较高。采用气相色谱法(GC)对生产工艺中用到的溶剂进行了筛选和测定,部分样品中残留溶剂丙酮的含量接近限值。结论:目前国产注射用头孢噻吩钠的产品质量能符合现行标准要求;而探索性研究提示现行标准存在缺陷,未能有效分离并控制毒性杂质头孢噻吩3-位置异构体和杂质A,不能全面反映产品的质量,需进一步完善检验标准中针对性指标的设置。Objective： To assess the current quality of domestic cefalotin sodium for injection and to complete the items to be tested in the quality standard. Methods： According to the 2013 annual general requirements of national drug assessment programs,46 testing samples were inspected by the current statutory standards. At the same time,the test methods of the related substances,metals,residual solvent were established and improved by exploratory research. Results： Statutory inspection： the qualified rate of 46 cefalotin sodium for injection was 100%. Exploratory research： the impurity A assigned by current domestic and foreign pharmacopoeias was wrong; cefalotin 3- isomer was found for the first time and the quantitative method was also established. According to the result of zebrafish embryo acute toxicity test and acute toxicity in mice,the relative toxicity of impurities was in the following order： cefalotin 3-isomer 〉 impurity A 〉 impurity B 〉 cefalotin. Metal elements possibly existing in injection were screened by inductively coupled plasma optical emission spectrometry（ ICP- OES） and inductively coupled plasma mass spectrometry（ ICP-MS）,and zinc was detected in high content. Organic solvents used in production process were screened by gas chromatography（ GC）,and the content of acetone in some samples was close to the limit. Conclusion： The quality of domestic cefalotin sodium for injection meets the requirement of current statutory standard. On the other hand,exploratory research results suggest that the current standards have defects in that toxic impurities of cefalotin 3- isomer and impurity A has not effectively separated and controlled. The current standard should be further improved.

关 键 词：注射用头孢噻吩钠 质量评价 杂质谱 杂质A 头孢噻吩3-位置异构体 斑马鱼胚胎急性毒性研究 残留溶剂丙酮 金属杂质 

分 类 号：R917[医药卫生—药物分析学]