2.2. Method of determination of pKa values

Alendronate sodium solution (0.01 mol/L) and sodium hydroxide titrant (0.1 mol/L) were prepared by distilled water respectively, and the latter was calibrated by potassium hydrogen phthalate that had been dried to constant weight at 105 °C before use.

The acid dissociation constants were determined by titrating 20.00 mL of alendronate sodium solution with standardized NaOH solution. The pH value of alendronate sodium solution was adjusted to 1.38 using HCl solution (0.1 mol/L) before titration. When a few drops of NaOH solution were dropped into the beaker, the volume and the pH value were recorded when they were unchangeable. The procedures mentioned above were repeated until the pH value rose to 13. Finally, 98 of the titration data were obtained for each experiment.