Determination of pKa values of alendronate sodium in aqueous solution by piecewise linear regression based on acid-base potentiometric titration

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• 作者：Jing Ke^a ; Hanfei Dou^a ; Ximin Zhang^b ; Dushimabararezi Serge Uhagaze^a ; Xiali Ding^a ; Yuming Dong^a ; ^{dongym@lzu.edu.cn}
• 关键词：Dissociation constants ; Alendronate sodium ; Distribution curve ; Piecewise linear regression ; Acid-base potentiometric titration
• 刊名：Journal of Pharmaceutical Analysis
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：6
• 期：6
• 页码：404-409
• 全文大小：787 K
• 卷排序：6

文摘

As a mono-sodium salt form of alendronic acid, alendronate sodium presents multi-level ionization for the dissociation of its four hydroxyl groups. The dissociation constants of alendronate sodium were determined in this work by studying the piecewise linear relationship between volume of titrant and pH value based on acid-base potentiometric titration reaction. The distribution curves of alendronate sodium were drawn according to the determined pKa values. There were 4 dissociation constants (pKa1=2.43, pKa2=7.55, pKa3=10.80, pKa4=11.99, respectively) of alendronate sodium, and 12 existing forms, of which 4 could be ignored, existing in different pH environments.