Study of system properties in reversed-phase liquid chromatography for binary and ternary solvent mobile phase compositions using the solvation parameter model

System maps for the individual system constant of the solvation parameter model and five binary solvent containing 20–70% (v/v) acetonitrile, acetone, methanol, 2-propanol, and tetrahydrofuran on a single octadecylsiloxane-bonded silica column (Luna C18) are used to provide insight into the variation of system properties with mobile phase composition and solvent type. Selectivity differences are dominated by variation in solute size and hydrogen-bond basicity with solvent-dependent variation in dipole-type and hydrogen-bond acid interactions. Interactions involving lone pair electrons are important only in the case of the alcohols and to a lesser extent tetrahydrofuran. Selectivity differences are also dependent on solvent strength. To expand the selectivity space four ternary solvent systems (acetonitrile-methanol-water, acetonitrile-2-propanol-water, methanol-tetrahydrofuran-water, and tetrahydrofuran-2-propanol-water) 1:1:2% (v/v) containing 50% (v/v) total organic solvent are compared with the binary solvent systems at the same organic solvent composition. There is no simple model that links the system properties of the ternary solvents to the binary solvent systems, but it is demonstrated that the ternary solvent systems expand the selectivity space available for reversed-phase separations. The solvation properties of the bulk organic solvents provide insufficient information to predict selectivity in RPLC because of the dominant contribution of water and effects related to the selective solvation of the stationary phase and possible changes in the solvent-dependent microstructure of the mobile phase.