We have developed a fast and accurate potentiometric method to characterize the pH-dependent, Schiffʼs base formation equilibria in waterâ organic cosolvent mixtures. This method has been applied to the reaction between pyridoxal 5â ²-phosphate and hexylamine in waterâ dioxane. We have found that, at neutral and basic pH, the Schiffʼs base is more stable in the lower polarity media. It is suggested that this is a secondary effect, due to the fact that Schiffʼs base formation is accompanied by charge neutralization.