Solubility by Potentiometry

Potentiometry is a further technique used to measure aqueous solubility in discovery, although throughput limitations mean that this technique is used most often later in the LO stage. Potentiometric approaches specifically measure intrinsic solubility, which is the solubility of the neutral form of the molecule [38], 

With the potentiometric approach, determination of intrinsic solubility is based upon the measurement of the pH shift caused by compound precipitation during acid-base titration of ionizable compounds. Two commercial potentiometric methods currently available are pSol [30, 39] and Cheqsol [40-42], In the pSol method developed by Avdeef, a minimum of three titrations in the direction of dissolution are performed. Normal pH versus volume titration plots are reexpressed as Bjerrum plots, that is, average number of bound protons versus pH. The Bjermm plots enable the shift in compound pKa to be more readily observed and are used to determine intrinsic solubility (S0) via Equation 2.5  

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