In most cases the average level of accuracy and precision in a HILIC analysis is less than typical values obtained by reversed-phase (RP). The accuracy and precision of a HILIC analysis is strongly influenced by the equilibration time if a gradient method is used.

In addition, Aqueous Normal Phase (ANP) is more suitable than HILIC in terms of accuracy and precision. The reason for this is that in HILIC, the water layer that is thought to be primarily responsible for retention is slow to fully equilibrate and sometimes variable from run to run.