Physicochemical profiling of drug candidates using capillary-based techniques

Abstract

In drug discovery and early drug development, the amount of new chemical entity available is often limited preventing detailed physicochemical profiling and ADME characterization. Capillary-based techniques constitute an alternative to current methods requiring only microgram quantities for analysis. The use of capillary-based techniques for physicochemical profiling of drug development candidates is reviewed. Focus is on affinity methods based on capillary electrophoresis, such as mobility shift affinity capillary electrophoresis, electrokinetic chromatography, frontal analysis capillary electrophoresis and pre-equilibrium capillary zone electrophoresis, and on Taylor dispersion analysis. These approaches are efficient for quantifying ionization constants (pK a ), lipophilicity, distribution phenomena in relation to micelles, microemulsions and liposomes, protein binding, and interactions with pharmaceutical excipients. Taylor dispersion analysis can be used to quantify binding constants when both binding partners are neutral as well as to determine drug substance diffusivity and hydrodynamic radius.