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

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.