Abstract
Many solvents and additives are used to prepare mobile phases in liquid chromatography (LC). Also, mixtures of solvents at different ratios are used to modify the mobile-phase properties. This can make solvent selection for method development a puzzling task, unless suitable guidelines are followed. This chapter summarizes the most common strategies used by skilled chromatographers in reversed-phase, normal-phase, and hydrophilic interaction LC. These are based on considerations about the global polarity of solutes, stationary phase, and mobile phase, which determine the elution strength, and on the particular profile of the contributions of intermolecular interactions to the global polarity, which determines the selectivity. The optimization of selectivity using isoeluotropic mixtures on the rational basis provided by solvent-selectivity profiles and by systematic trial-and-error procedures in the isocratic and gradient elution modes is described. The modification of the selectivity by using combinations of solvents is discussed. Additional considerations for mobile-phase selection, including computer-assisted interpretive optimization, sustainability criteria, and use of high temperature, are also commented.
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