eCite Digital Repository

Internal standard capillary electrophoresis as a high-throughput method for pKa determination in drug discovery and development

Citation

Cabot, JM and Fuguet, E and Roses, M, Internal standard capillary electrophoresis as a high-throughput method for pKa determination in drug discovery and development, ACS Combinatorial Science, 16, (10) pp. 518-525. ISSN 2156-8952 (2014) [Refereed Article]

Copyright Statement

Copyright 2014 American Chemical Society

DOI: doi:10.1021/co500059p

Abstract

A novel high-throughput method for determining acidity constants (pKa) by capillary electrophoresis (CE) is developed. The method, based on the use of an internal standard (IS-CE), is implemented as a routine method for accurate experimental pKa determination of drugs undergoing physicochemical measurements in drug discovery laboratories. Just two electropherograms at 2 different pH values are needed to calculate an acidity constant. Several ISs can be used in the same buffer and run to enhance precision. With 3 ISs, for example, the pKa of the test compound (TC) can be obtained in triplicate in less than 3 min of electrophoresis. It has been demonstrated that the IS-CE method eliminates some systematic errors, maintaining, or even increasing the precision of the results compared with other methods. Furthermore, pH buffer instability during electrophoretic runs is not a problem in the IS-CE method. It is also proved that after 16 h of electroseparation using the same buffer vial, pH may change by around one unit; but the pKa calculated by the IS-CE method remains constant. Thus, IS-CE is a powerful high-throughput method for pKa determination in drug discovery and development.

Item Details

Item Type:Refereed Article
Keywords:pKa, electrophoresis, physico-chemical properties, method development
Research Division:Chemical Sciences
Research Group:Analytical Chemistry
Research Field:Analytical Spectrometry
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Mathematical Sciences
Author:Cabot, JM (Dr Joan Cabot Canyelles)
ID Code:104639
Year Published:2014
Web of Science® Times Cited:7
Deposited By:Chemistry
Deposited On:2015-11-17
Last Modified:2017-11-01
Downloads:0

Repository Staff Only: item control page