摘要
目的:通过对上市注射用头孢呋辛钠检验与研究,从安全性、有效性和质量可控性等方面对其进行全面质量分析评价。方法:依据现行法定质量标准,对全国范围内的注射用头孢呋辛钠进行标准检验,运用多种统计学方法,分析国内注射用头孢呋辛钠的质量总体水平,比较不同生产企业产品质量;根据专题调研、文献检索和标准检验结果及分析等情况,开展了有关物质、头孢呋辛聚合物、残留溶剂、2-乙基己酸、不同生产工艺与稳定性等5个方面的探索研究。结果:本次抽验中涉及的169批次样品标准检验,不合格率为3.0%。其中,2批样品性状不符合规定,4批溶液的颜色超标,1批溶液的澄清度不符合规定。建立了本品杂质谱,明确杂质A,B,C,D,H,I及另26种未知杂质为国内注射用头孢呋辛钠的主要杂质种类及其量值;建立了新的TSK凝胶色谱法对169批样品进行头孢呋辛聚合物的测定;国内头孢呋辛钠原料残留溶剂控制较好,2-乙基己酸的残留控制在较低范围内;高纯氮气保护工艺更优。结论:注射用头孢呋辛钠现行标准基本可行,质量状况较好,企业生产工艺成熟,质量总体水平稳定性好,但有提升空间。建议继续提高质量标准,确认杂质种类,并对主要杂质分别设定控制指标;采用更具灵敏度和准确度的方法检查头孢呋辛聚合物;采用客观量化的技术手段及方法,对溶液的颜色进行检查;高纯氮气保护工艺更优,应督促有关企业积极改进生产工艺,优选工艺参数,提高本品的稳定性,保证药物安全有效和质量可控;开展针对溶液颜色的专项检查,并加强流通使用环节的环境控制。
Objective： To comprehensively evaluate the qualities of cefuroxime sodium for injection. Methods： All the samples were examined by current standards, and the results were statistically analyzed to assess the overall level of quality. The product qualities from different manufacturing enterprises were compared. Accord- ing to special investigations, literature search and analysis of the testing results, we performed an exploratory study for detecting related substances, cefuroxime polymers, residual solvents, 2-ethylhexanoic acid, and stabilities un- der different production processes. Results： By current standards, in 169 batch samples, 5 failed （3.0%） , and the main causes of failure were color and clarity of solution. The impurity spectrum was established, and the main impurities in cefuroxime sodium were the impurities A, B, C, D, H and I as well as other 26 kinds of impurities.Their average values were calculated. A method of TSK gel permeation chromatography was established for the de- termination of the polymers of cefuroxime, and 169 batches of samples were tested by this method. The manufactur- ing enterprises had well controlled quantity of residual solvents and 2-ethylhexanoic acid in the raw materials. The process filling nitrogen to push out the air in powder could keep the medicine＇s color and related substance from changing and protect the therapeutic effect. Conclusion： Current standards can basically control the quality of the drugs, and the quality of cefuroxime sodium for injection is satisfactory but needs improvement. It is suggested to improve quality standards, definite the kinds of impurity and control some main impurities. The polymers of cefu- roxime should be detected by more sensitive and accurate methods, and the color of solution should be inspected u- sing more objective techniques. Furthermore, we also suggest that domestic enterprises should further optimize their productive technologies, and improve the stability and effectiveness of the drug. At the same time, it is necessary to carry out the special inspection for color of solution, and to strengthen the control of link in circulation and use.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2014年第5期518-522,共5页
Chinese Journal of New Drugs
基金
国家"重大新药创制"科技重大专项(2011ZX09303-001)
关键词
注射用头孢呋辛钠
质量分析
杂质谱
cefuroxime sodium for injection
quality assessment
impurity spectrum
