The performance of 1‐ethyl‐3‐methylimidazolium tetrafluoroborate ionic liquid as mobile phase additive in HPLC‐based lipophilicity assessment

Ionic liquids have been widely used as green alternative mobile phase additives to shield the residuals silanols groups and modify the stationary/mobile phase HPLC systems. The present study aimed to evaluate the performance of the ionic liquid 1‐ethyl‐3‐methylimidazolium tetrafluoroborate ([EMIM][BF4]) in producing extrapolated log k w indices suitable to substitute for octanol–water log P or log D values. The effect of [EMIM][BF4] was investigated for a set of basic and neutral drugs using two different columns, BDS and ABZ + . [EMIM][BF4] was added simply alone or in combination with n ‐octanol and was compared with the conventional masking agent n ‐decylamine. [EMIM][BF4] reduced the retention by suppressing silanophilic interactions, althoug to a lower extent than n ‐decylamine. Addition of n ‐octanol further decreased the retention by shielding silanol sites on BDS and/or interacting with polar groups through hydrogen bonding on ABZ + . Log k w /log D 7.4 relationships proved moderate compared with those derived upon addition of n ‐decylamine. They were considerably improved upon the introduction of protonated fraction F + in the correlation, reflecting ion pair formation between the chaotropic anion [BF4] ‐ and the protonated basic compounds. In this aspect, the ionic liquid [EMIM][BF4], although efficient as a masking agent, cannot be recommended as mobile phase additive to reproduce octanol–water partitioning. Copyright © 2010 John Wiley & Sons, Ltd.