盐酸莫西沙星注射液的质量分析

Quality analysis of moxifloxacin hydrochloride injection

目的评价盐酸莫西沙星注射液的质量现状。方法采用调研、文献检索、法定标准检验结合探索性研究的方式,对包括原研企业在内的5家企业生产的79批盐酸莫西沙星注射液的质量进行比较分析,通过对溶液颜色、对映异构体、有关物质、杂质谱及无菌保障水平等关键质量属性进行考察,分析不同企业产品的质量差异及质量标准的合理性。结果通过法定标准检验,79批盐酸莫西沙星注射液合格率为100%,但该品种存在原研制剂的国外执行标准与进口注册标准的颜色描述不一致,部分项目检验方法及限度不统一,部分标准存在溶液颜色、对映异构体项目缺失等问题。通过探索性研究明确了盐酸莫西沙星注射液的色系,优化了对映异构体以及有关物质检查方法,采用LC/MS对杂质结构进行推断,并对其来源进行了归属。调研的6家企业均采用终端灭菌,且为过度灭菌,但在微生物过程控制方面仍有提升空间。结论盐酸莫西沙星注射液总体质量较好,但仿制制剂在杂质控制水平上与原研制剂仍存在一定差距,建议国内仿制药企业优化合成及工艺路线并提高无菌保障水平以提高产品质量;现行标准有待统一和提高。

Objective To evaluate the quality condition of moxifloxacin hydrochloride injection.Methods The investigation,literature retrieval,statutory standard tests combined with the exploratory researches were used to examine samples and evaluate the quality condition of 79 batches of moxifloxacin hydrochloride injection produced by five manufacturers.Critical quality attributes such as the color of solution,enantiomers,related substances,the impurity profile,and the sterility assurance level were inspected to analyze the quality differences of products from different manufacturers and the rationality of quality standards.Results Statutory tests showed that the qualified rate was 100%for the 79 batches samples.However,there was a discrepancy in the color description between domestic and foreign standards of innovative drugs.Analysis methods and limits of current standards were not uniform and some of them were lack of items such as color of solution and enantiomers.In exploratory research,the hue of the test solution was determined,new analysis methods of enantiomers and related substances were established,and the structures and sources of related substances were confirmed by using LC/MS.The six manufacturers that we investigated adopted terminal sterilization and over sterilization,but the level of microbial process control still needs to be improved.Conclusion The quality of moxifloxacin hydrochloride injection was good,but a difference in the level of impurities was found between generic products and innovative drugs.In order to improve product quality,it is recommended that the production processes of raw materials and preparations should be optimized and the level of sterility assurance needs to be improved by domestic manufacturers;the current statutory standards should be unified and further improved.