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.
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