药用气雾剂辅料1,1,1,2-四氟乙烷及其主要杂质国家对照品的研制  

Establishment of the national reference standards of 1,1,1,2-tetrafluoroethane as the excipient of medicinal aerosol and its impurities

作　　者：赵燕君 仪忠勋 谢兰桂[1] 肖新月[1] 杨会英[1] 孙会敏[1] ZHAO Yan-jun;YI Zhong-xun;XIE Lan-gui;XIAO Xin-yue;YANG Hui-ying;SUN Hui-min(NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,National Institutes for Food and Drug Control,Beijing 100050,China)

机构地区：[1]国家药品监督管理局药用辅料质量研究与评价重点实验室,中国食品药品检定研究院,北京100050

出　　处：《中国新药杂志》2023年第16期1677-1683,共7页Chinese Journal of New Drugs

基　　金：中国食品药品检定研究院中青年发展研究基金课题资助项目(2020C2)。

摘　　要：目的:研制药用气雾剂辅料1,1,1,2-四氟乙烷及其主要杂质的国家对照品,为加强其质量控制提供依据。方法:对1,1,1,2-四氟乙烷及其主要杂质1,1,2,2-四氟乙烷、五氟乙烷、五氟氯乙烷、1,1,1-三氟乙烷进行液态直接分装,采用IR,MS,MR技术进行结构确证,库仑法测定水分,闭水法测试包装密封性,质量平衡法确定各物质含量,并分别用F检验和线性拟合进行均匀性、稳定性考察,同时对主成分1,1,1,2-四氟乙烷进行多家实验室协作标定定值。结果:研制的1,1,1,2-四氟乙烷及其主要杂质1,1,2,2-四氟乙烷、五氟乙烷、五氟氯乙烷、1,1,1-三氟乙烷标准值分别为100.0%,99.9%,99.7%,99.2%,99.9%,具有良好的均匀性和稳定性。结论:本研究首次制备了1,1,1,2-四氟乙烷及其主要杂质国家对照品,其中1,1,1,2-四氟乙烷可用作含量测定用对照品,其他物质可作为有关物质检查用对照品。Objective:To develop the national reference standards of 1,1,1,2-tetrafluoroethane as the excipient of medicinal aerosol and its impurities thus to improve the standard of quality control.Methods:The national reference standards of 1,1,1,2-tetrafluoroethane and its main impurities 1,1,2,2-tetrafluoroethane,pentafluoroethane,pentafluorochloroethane and 1,1,1-trifluoroethane were sub-packaged in liquid state directly.The structures were confirmed by IR,MS and MR spectroscopy,the moisture was determined by Coulomb method,the tightness of the package was confirmed by immersion in water.The content of each substance was calculated by mass balance method.Homogeneity and stability were investigated by F test and linear fitting respectively,and the content of 1,1,1,2-tetrafluoroethane was confirmed by multiple laboratories simultaneously.Results:The contents of 1,1,1,2-tetrafluoroethane,1,1,2,2-tetrafluoroethane,pentafluoroethane,pentafluorochloroethane and 1,1,1-trifluoroethane were 100.0%,99.9%,99.7%,99.2%,and 99.9%,respectively,with good homogeneity and stability.Conclusion:In this study,the national reference standards of 1,1,1,2-tetrafluoroethane and its main impurities were developed for the first time,where 1,1,1,2-tetrafluoroethane can be applied for content determination,and the other substances can be applied for the inspection of related substances.

关 键 词：药用气雾剂 抛射剂 1 1 1 2-四氟乙烷 五氟乙烷 五氟氯乙烷 1 1 1-三氟乙烷 对照品 

分 类 号：R932[医药卫生—生药学]