Understanding and manipulating the separation in hydrophilic interaction liquid chromatography

Hydrophilic interaction liquid chromatography (HILIC) has emerged as a valuable complimentary technique to reversed-phase (RP), being especially suited for the analysis of polar and ionised solutes, which are difficult to retain in RP. For solutes amenable to both separation mechanisms, HILIC provides a different selectivity to RP, and also offers possibilities as an orthogonal mechanism for 2-dimensional LC when combined with RP. HILIC has further advantages of lower column back pressures, and increased sensitivity with mobile phase evaporative detectors such as electrospray mass spectrometry. This review covers progress in our understanding of the HILIC technique, principally over the last ten years, including the classification of columns, the factors that control retention and selectivity, and attempts to model the separation process and its kinetics.