Performance to burn? Re-evaluating the choice of acetonitrile as the platform solvent for analytical HPLC

Acetonitrile is by far the preferred organic solvent for use in Reversed Phase High Performance Liquid Chromatography (RP-HPLC) today, owing to an excellent combination of physical properties of this solvent that are favorable for chromatography (viscosity, UV absorbance cutoff, boiling point). In recent years, improvements in both instrument and stationary phase technologies have greatly enhanced the performance of routine laboratory HPLC, leading to an excess of performance for many users. In this study we re-examine the choice of acetonitrile as the platform organic solvent for HPLC, addressing the question of whether greener solvents such as ethanol could potentially replace acetonitrile in some instances.