Work

Internal Standard Capillary Electrophoresis as a High-Throughput Method for pKaDetermination in Drug Discovery and Development

Year: 2014

Type: article

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.

Source: ACS Combinatorial Science

DOI: 10.1021/co500059p

Authors: Joan M. Cabot, Elisabet Fuguet, Martí Rosés

Institutions: Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona

Language: English

Topic: Microfluidic and Capillary Electrophoresis Applications

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

Open Access status: green

Funders: Generalitat de Catalunya, Ministerio de Economía y Competitividad, European Regional Development Fund

Awards: G1014400177, G1111373570