注射用盐酸甲氯芬酯杂质谱与其生产工艺的相关性研究  

Correlation study between production process and impurity profile of meclofenoxate hydrochloride for injection

作　　者：王琳[1] 吴兆伟[1] 王铁松[1] 谢立[1] 胡琴[1] 

机构地区：[1]北京市药品检验所,北京100035

出　　处：《药物分析杂志》2017年第7期1304-1308,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：北京市科技计划(Z131100005613032)

摘　　要：目的:研究注射用盐酸甲氯芬酯的杂质谱及其与生产工艺的相关性。方法:用液相色谱进行杂质定量检测,根据液质联用分析和定向合成确证杂质结构,采用质量平衡法标化杂质对照品。通过对9家企业66批样品的进一步实验与综合分析推断杂质的来源,并根据杂质形成的原因提出针对性防控措施。结果:注射用盐酸甲氯芬酯的主要降解杂质为杂质A、B和C,其中杂质A为水解杂质,主要为制剂冷冻干燥生产工艺中引入,与配制过程中的溶液pH,配制温度和时间具有正相关。杂质B和杂质C为醇解杂质,主要为原料药合成工艺中引入,与工艺中使用的低级醇类有关。结论:本实验的研究方法可对注射用盐酸甲氯芬酯的杂质进行更全面的检测,为改进工艺提供依据,对提高产品质量具有重要意义。Objective： To study impurity profiling of meclofenoxate hydrochloride for injection and the correlation with produetion proeess. Methods：The liquid chromatography was used for impurity detection. The structure of impurities was confirmed with liquid chromatography-mass spectrometry analysis and oriented synthesis. The mass balance method was used to prepare the reference standards of impurities. Further experiments and comprehensive analyses were made to infer sources of impurities in 66 batches of samples from 9 manufacturers and the specific prevention and control measures were proposed according to the causes of impurity formation. Results： The main degradations in meclofenoxate hydrochloride injeetion were impurities A~ B and C. The impurity A was hydrolysis impurity, which was mainly introduced in freeze-drying process. Impurity A was related to pH of solution, temperature and time of preparation process. The impurity B and C were aleoholysis impurities, which were mainly introduced in synthesis process of bulk drug. B and C were related to low alcohol solution used in process.Conclusion： The study is suitable for profiling the impurities in meclofenoxate hydrochloride for injection. It is useful for improving process procedure and enhancing quality control.

关 键 词：盐酸甲氯芬酯 杂质谱检测 杂质结构确证 生产工艺 杂质工艺相关性 

分 类 号：R917[医药卫生—药物分析学]