气雾剂抛射剂替代物1,1,1,2-四氟乙烷的关键质量属性酸碱度研究  

Study on the key quality properties of acidity or alkalinity in pharmaceutical 1,1,1,2-tetrafluoroethane

作　　者：赵燕君 许新新 田霖[1] 仪忠勋 孙会敏[1] 杨会英[1] ZHAO Yan-jun;XU Xin-xin;TIAN Lin;YI Zhong-xun;SUN Hui-min;YANG Hui-ying(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：《药物分析杂志》2022年第9期1659-1666,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：药用吸入气雾剂用HFA-134a质量标准的建立(C/Ⅲ/S/17/162)。

摘　　要：目的:分别用酸碱滴定和电导率法对气雾剂抛射剂替代物HFA-134a的关键质量属性酸碱度进行分析,为其质量标准的制修订、产品质量控制提供参考。方法:采用3种酸碱指示剂确定样品的酸碱属性,选择合适的萃取液,用酸碱滴定和电导率法分别检测4个厂家24批样品的酸碱含量并比较两种方法的差异。结果:4个厂家的24批样品均显碱性,无论用酸碱滴定还是电导率法,用二甲基亚砜/异丙醇/水混合溶剂为萃取液均比用去离子水为萃取液能更好的吸收HFA-134a中的H^(+)或OH^(-),检测结果更准确。用配对样本t检验及Wilcoxon符号秩和检验分析2种方法的检测结果,无显著性差异,但电导率法的离散性较酸碱滴定法大。结论:结合1,1,1,2-四氟乙烷的生产工艺、检测结果及其对用药安全的影响,建议对其进行质量控制时不仅要关注酸度,也要控制碱度。Objective: To analyze the acidity or akalinity in pharmaceutical 1, 1, 1, 2-tetrafluoroethan(HFA-134 a) by the method of acid-base titration and conductivity, respectively. Methods: Three acid-base titration indicators were used to test whether the sample is acidic or alkaline. A suitable extraction solvent was selected and the acidity or alkalinity of 24 batches of samples from four manufacturers were detected by acid-base titration or conductivity change, and the differences between the two methods were compared. Results: All the 24 batches of samples from four manufacturers were alkaline. The H^(+)or OH^(-)in HFA-134 a was absorbed better and the result was more accurate with dimethyl sulfoxide(DMSO), isopropanol and water extraction solvent than deionized water solvent in both acid-base titration and conductivity changes. The results analyzed by t test of paired samples and Wilcoxon signed ranks test showed that there was no significant difference between two methods, but the resultsmeasured by the conductivity are more discrete than acid-base titration. Conclusion: In the quality control of HFA-134 a, not only the acidity but also the alkalinity should be controlled.

关 键 词：药用辅料 抛射剂 四氟乙烷 HFA-134a 酸碱度 

分 类 号：R917[医药卫生—药物分析学]