Abstract

Capillary electrophoresis (CE) with organic solvents has gained special interest in pharmaceutical analysis as it offers an alternative to overcome problems with the solubility especially of lipophilic analytes in aqueous solutions. However, beside the solubility of the compounds (typical pharmaceuticals are weak acids and bases, that can be present in ionic and molecular form as well) other properties and variables relevant for capillary electrophoretic separations are influenced by the solvent. In the present paper the role of the solvent on these quantities is discussed from a more general point of view. This discussion includes the influence on the ionic mobility and its different concentration dependence for solvents like methanol, acetonitrile, propylene carbonate, formamide, N,N-dimethylformamide, N,N-dimethylacetamide and nitromethane in comparison with water. It also includes the explanation of the partially extreme change in the pK values of the weak acids and bases when water is replaced by the organic solvent, by taking into account the stabilization of the individual charged and uncharged particles involved in the protolysis equilibria. For a better comprehension of the role of the solvent on the resolution of the analytes, also its influence on the separation efficiency has to be elucidated. For this purpose, the function of the solvent concerning the inevitable peak broadening due to diffusion and the limitations of the achievable plate number is explicated based on a sound background. As the understanding of the effect of the solvent on the relevant properties of the analytes and the constituents of the background electrolyte, and on the properties of the separation system is a prerequisite for a systematic planning of the nonaqueous CE experiment and the critical evaluation of the result obtained, the present paper tries to contribute to this goal.

Keywords: Capillary electrophoresis, organic solvents, nonaqueous, NACE, pharmaceutical, solubility, migration, dispersion, efficiency, plate number, analysis time.