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。
赵燕君, 许新新, 田霖, 仪忠勋, 孙会敏, 杨会英
. 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*[J]. 药物分析杂志, 2022
, 42(9)
: 1659
-1666
.
DOI: 10.16155/j.0254-1793.2022.09.20
Objective: To analyze the acidity or akalinity in pharmaceutical 1, 1, 1, 2-tetrafluoroethan(HFA-134a) 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-134a 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 results measured by the conductivity are more discrete than acid-base titration. Conclusion: In the quality control of HFA-134a, not only the acidity but also the alkalinity should be controlled.
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