A rapid method for pKa determination of drugs using pressure-assisted capillary electrophoresis with photodiode array detection in drug discovery
A rapid method for pKa determination of drugs using pressure-assisted capillary electrophoresis with photodiode array detection in drug discovery
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DOI：
10.1002/jps.10087
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发表时间：
2002-04-01
影响因子：
3.8
通讯作者：
Asakawa, N
中科院分区：
文献类型：
--
作者：
Ishihama, Y;Nakamura, M;Asakawa, N
建立了一种压力辅助毛细管电泳联用光电二极管阵列检测器快速筛选候选药物PK(A)的方法。在CE分析过程中施加压力，在不到1分钟的时间内完成一次CE运行，并通过非线性回归拟合软件分析获得的pH-度量迁移率漂移和pH-度量UV光谱，以确定pK(A)值。77种药物的82个离子官能团的pK(A)值与其他常规方法的pK(A)值之差在0.25个单位以内。在96孔微孔板上可在1天内测定96种化合物在二甲基亚砜溶液中的pK(A)值。本方法能快速、准确地测定pK(A)值。(C)2002年Wiley-Liss，Inc.
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. (C) 2002 Wiley-Liss, Inc.