A binary-like approach for the computer assisted method development of isocratic and programmed ternary solvent elutions in reversed-phase liquid chromatography

A specific tool to enable exploration of multisolvent isocratic and programmed elutions for the computer assisted method development of reversed-phase liquid chromatography separations is described. The tool is purposely identical to those used in the optimization of binary solvent systems, which are by far the most commonly used by chromatographers. Existing data from failed binary solvent optimization processes are reused to explore ternary solvent systems with a few additional isocratic and programmed runs. This allows the development of efficient retention models for ternary systems, although the work of the chromatographer remains identical to that for optimization of binary systems. The retention models are used to develop an unattended optimization process and finally, the chromatographer selects the most satisfactory solution for testing and implementing in routine analysis. The process is exemplified with a mixture of 12 compounds that cannot be separated satisfactorily in aqueous binary solvent systems with methanol and acetonitrile as modifiers.