对卤米松/三氯生乳膏中有关物质检查方法的思考  

Thoughts on determination method of the related substances in halometasone/triclosan cream

作　　者：赵敬丹 陈阳 刘浩 金薇 乐健 ZHAO Jing-dan;CHEN Yang;LIU Hao;JIN Wei;LE Jian(NMPA Key Lab for Quality Analysis of Chemical Drug Preparations,Shanghai Institute for Food and Drug Control,Shanghai 201203,China)

机构地区：[1]上海市食品药品检验研究院、国家药品监督管理局化学药品制剂质量分析重点实验室,上海201203

出　　处：《药物分析杂志》2024年第7期1233-1237,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:通过卤米松/三氯生乳膏中最大单个未知杂质的结构推测,探讨进口注册标准的合理性。方法:采用国家食品药品监督管理局进口药品注册标准JX20080304中有关物质项下的色谱条件对样品进行杂质检查;采用USP三氯生项下的方法对样品中的二噁英类物质进行检查;采用LC-Q TOF/MS对样品中的最大单个未知杂质进行推测。结果:按照JX20080304测定,以卤米松计,样品中最大单个杂质(RRT 0.67)检出量为2.5%,超出标准规定的1.0%;结合三氯生对照品溶液的色谱保留行为,推测上述杂质可能来源于三氯生;结合杂质的MS信息,推测可能为三氯生的工艺杂质。结论:对于复方制剂,建议对主要相关成分中涉及的杂质分别进行控制,并根据安全性数据进行有效评估,以保证制剂产品质量的稳定性和临床用药的安全性。Objective:To analyze the structure of the maximum impurity in halometasone/triclosan cream and discuss the rationality of the current registered standard for imported drugs.Methods:The related substances in halometasone/triclosan were detected according to JX20080304,and dioxins were determined according to USP.Finally,the possible structures of the maximum impurity were characterized by LC-Q TOF/MS.Results:The results showed that the maximum unknown impurity(RRT 0.67),calculated according to halometasone was OOS(1.0%)at 2.5%.The peak was related to triclosan through comparing with the chromatography behavior of triclosan in reference substance solution.MS information indicted the process impurities of triclosan.Conclusion:For compound preparations,to ensure the stability and safety of the product,the impurities relevant to different components should be controlled separately at rational limit based on safety data.

关 键 词：卤米松 三氯生 杂质 二噁英 复方制剂 有关物质 安全性 质谱 

分 类 号：R917[医药卫生—药物分析学]