Evidence suggests that the retention mechanism in HILIC is complex, and consists of a combination of:
- Hydrophilic partitioning of the analyte between the aqueous-rich layer and the bulk of the mobile phase
- Hydrogen bonding between polar functional groups and the stationary phase
- Electrostatic interactions on ionized functional groups
Additionally, van der Waals interactions between the hydrophobic portions of the bonded ligands of the stationary phase and the non-polar part of the analytes may be present.