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HILIC (hydrophilic interaction liquid chromatography) columns are used to separate polar compounds that are too hydrophilic to be retained by a typical reversed phase column. In HILIC mode, the water acts as the strong solvent, and the organic solvent acts as the weak solvent (the opposite to reversed phase chromatography). This avoids the need for older techniques such as derivatization, ion pairing, and normal phase HPLC.

There are a wide variety of polar stationary phases that work in HILIC mode, with many columns generically described as HILIC. The oldest and most widely available HILIC phase is bare silica. Various bonded phases, including diol, amino, and zwitterionic provide alternative selectivity and improved reliability. Newer HILIC phases offer short equilibration times, excellent resolution, and good peak shape. 

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