Abstract
Many solvents are used to prepare mobile phases in liquid chromatography. Furthermore, mixtures of solvents are used in different proportions to modify the properties of the mobile phase. This can make their selection for method development a bewildering task unless proper guidelines are followed. This chapter summarizes the most common strategies used by experienced chromatographers in reversed-phase, normal-phase, and hydrophilic interaction liquid chromatography for mobile phase selection. The methodologies 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. Modification of selectivity through the use of solvent combinations is discussed. Additional considerations for mobile phase selection, including computer-assisted interpretive optimization, sustainability criteria, and the use of high temperature, are also discussed.
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