Ionic liquid-based liquid phase microextraction with direct injection for capillary electrophoresis

Abstract

Liquid–liquid microextraction using the water immiscible ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, EMIM NtfO 2, for the concentration and cleanup of basic compounds for analysis by CE has been investigated. Using an electrolyte comprising 1 mol/L alanine and 3 mol/L acetic acid, EMIM NtfO 2 could be directly injected into the capillary after liquid phase extraction. Using the basic dye chryisoidine, sensitivity enhancements approaching 1000-fold were obtained by mixing 20 μL of EMIM NtfO 2 with 1500 μL of aqueous sample, leaving only 5 μL of the undissolved ionic liquid which was used for injection into the CE. Lower more repeatable enhancement factors of 200-fold were obtained with slightly larger initial 25 μL volumes of EMIM NtfO 2 due to the larger residual volume of ionic liquid which made handling easier. This could be extended to basic pharmaceuticals, and the extraction of clozapine and its two active metabolites, nor-clozapine and clozapine-N-oxide, was demonstrated from urine with enrichment factors greater than 100 obtained. Handling of potentially more dangerous samples, such as serum, through in-vial extraction of clozapine and its metabolites and direct injection of the ionic liquid layer was also demonstrated with enhancements in sensitivity of 80. Limits of detection from 3 to 11 μg/L and 6 to 55 μg/L were obtained from urine and serum, respectively, which are sufficiently low to be useful for the determination of these pharmaceuticals clinically for therapeutic drug monitoring and for forensic toxicology.