Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Evaluation of a multiplexed capillary electrophoresis (CE) method for pK(a) measurements of organic compounds, including low solubility compounds, is presented. The method is validated on a set of 105 diverse compounds, mostly drugs, and results are compared to literature values obtained from multiple references. Two versions of the instrument in two different labs were used to collect data over a period of 3 years and inter-laboratory and inter-instrument variations are discussed. Twenty-four point aqueous and mixed cosolvent buffer systems were employed to improve the accuracy of pK(a) measurements. It has been demonstrated that the method allows direct pK(a) measurements in aqueous buffers for many compounds of low solubility, often unattainable by other methods. The pK(a) measurements of compounds with extremely low solubility using multiplexed CE with methanol/water cosolvent buffers are presented.