Towards the Expanded Use of Greener Approaches for Small Molecule Purification
Introduction
In recent years, an increased emphasis on greener alternatives to normal phase chromatography has driven the broader adoption of reversed-phase methods, and include efforts to identify more sustainable and less hazardous alternatives to acetonitrile. This work describes the optimization of methods (including “In-Column” dilution1) for the reversed-phase purification of a mixture of pharmaceutically relevant compounds spanning a range of hydrophobicities and pKa values.2
The evaluation of various conditions are presented, including an evaluation of the effect of particle size (5 vs 10 vs 20-25 μm) and highlighting the use of ethanol and ethanol/dimethyl carbonate (DMC) mixtures as greener alternatives to acetonitrile. The results suggest the viability of the use of ethanol and ethanol/dimethyl carbonate mixtures, and support the use of 10 μm particle size columns to maximize efficiency and recovery.
