title: The performance of 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid as mobile phase additive in HPLC-based lipophilicity assessment.
abstract: 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 logk(w) indices suitable to substitute for octanol-water logP or logD 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(+) . Logk(w) /logD(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.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens, Greece. cgiaginis@yahoo.gr
authors.forename: Costas
authors.initials: C
authors.lastname: Giaginis
authors.forename: Anna
authors.initials: A
authors.lastname: Tsantili-Kakoulidou
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry; D012044:Regression Analysis
chemical_list: C499119:1-ethyl-3-methylimidazolium tetrafluoroborate; D000588:Amines; D007093:Imidazoles; D052578:Ionic Liquids; D004364:Pharmaceutical Preparations; C004744:decylamine; D020003:1-Octanol