Abstract
We developed a rapid screening method for determination of pKa of candidate drugs by pressure-assisted capillary electrophoresis (CE) coupled with a photodiode array detector. Application of pressure during CE analysis allowed completion of one CE run in less than 1 min, and the obtained pH-metric mobility shifts as well as pH-metric UV spectrum were analyzed by a nonlinear regression fitting software to determine pKa values. The difference between pKa values by this method and by other conventional methods is within 0.25 units for 82 ionic functional groups of 77 drugs. The pKa values of 96 compounds in dimethylsulfoxide solution on a 96-well microplate could be measured in 1 day. Our method provides rapid and accurate determination of pKa value. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 933–942, 2002
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