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Updated: Oct 1, 2026

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
A rapid method for pKa determination of drugs using pressure-assisted capillary electrophoresis with photodiode array
Yasushi Ishihama1, Masahiro Nakamura, Toshinobu Miwa
1Analytical Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. yasushi@bmb.sdu.dk
Abstract:
We developed a rapid screening method for determination of pK(a) 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 pK(a) values. The difference between pK(a) values by this method and by other conventional methods is within 0.25 units for 82 ionic functional groups of 77 drugs. The pK(a) 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 pK(a) value.
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