3.1.1. Liquid-Liquid Extraction

LLE is the oldest method of extracting analytes. Unfortunately, despite the simplicity of performance, the method has many disadvantages. It is a very time- and work-intensive process, and the results depend on many additional factors, e.g., the physicochemical character of analytes, the type of extraction solvents, the extraction time and the temperature, which in turn cause reproducibility and repeatability problems. Furthermore, according to the current trend of designing more environmentally-friendly analytical methods, the use of toxic organic solvents should be reduced. As is well known, LLE does not meet this condition. In all probability, this was the reason why in regard to drug quantification in biological and environmental samples, traditional LLE extraction supported by IL modification was rarely considered. To the best of our knowledge, no reports have been published for biological applications, while only one paper can be found in the field of environmental investigations (Table 2).

**Table 2.** Summary of the IL applications in liquid-phase microextraction drugs from biological and environmental samples.


**Table 2.** *Cont.*


**Table 2.** *Cont.*




[C MIM]: 1-Ethyl-3-methylimidazolium; [C 2 MIM]: 1-butyl-3-methylimidazolium; [C 4 MIM]: 1-hexyl-3-methylimidazolium; [C 6 MIM]: 1-octyl-3-methylimidazolium; [MMIM]: 8 1,3-dimethylimidazolium; [C MPyrr]: 1-butyl-1-methylpyrrolidinium; [C 4 M4 3Amm]: 1-butyl-3-methylammonium; [IMIM]: 1-isopentene-3-methylimidazolium; [Nf2T]: bis(trifluoromethylsulfonyl)imid; [BF4]: tetrafluoroborate; [PF6]: hexafluorophosphate; [Cl]: chloride; [CH3(SO4)]: methylsulfate; HPCE: high performance capillary electrophoresis; HPLC-FL: high-performance liquid chromatography and fluorescence detection; HPLC-UV: high-performance liquid chromatography and ultraviolet detection; HPLC-DAD: high-performance liquid chromatography and diode array detection; LC-MS/MS: liquid chromatography—tandem mass spectrometry; UV: ultraviolet spectroscopy; HPLC-MWD: high-performance liquid chromatography and multiple wavelength detector; HPLC-PDA: high-performance liquid chromatography and photo-diode array detector; SFIS: stopped-flow injection spectrofluorimetry; TCIL-DLPME: temperature-controlled ionic liquid dispersive liquid phase microextraction; [C6NH MPyrr]: 1-(6-aminohexyl)-1-methylpyrrolidinium; 2 [TFP]: tris(pentafluoroethyl)trifluorophosphate; [ECMMPyrr]: 1-ethoxycarbonylmethyl-1-methylpyrrolidinium; [MOEDEAmm]: methoxyethyl-dimethyl-ethylammonium; [MOEMIM]: 1-methoxyethyl-3-methylimidazolium; [MOEMMO]: 1-methoxyethyl-1-methylmorpholinium; [MOPMPP]: 1-methoxypropyl-1-methylpiperidinum; [Aliquat+]2[MnCl4 2−]: aliquat tetrachloromanganate(II); [C MAmm]: methyltrioctylammonium; [P 8 6,6,6,14+]: trihexyltetradecylphosphonium; TUV: tunable ultraviolet detection; UHPLC: ultra-high pressure liquid chromatography; [MOEDEAmm]: ethyl-dimethyl-(2-methoxyethyl)ammonium; [NEMMP]: ethyl-dimethyl-propylammonium; MADLLME: microwave-assisted dispersive liquid–liquid microextraction; [TMG]: 1,1,3,3-tetramethylguanidine; [TEMPO]: 2,2,6,6-tetramethyl piperidine 1-oxyl free radical; IL-AF-μ-EME: Ionic liquid-impregnated agarose film two-phase micro-electrodriven membrane extraction; IL-ATPF: Ionic liquid–salt aqueous two-phase flotation; [DI-SPME]: direct-immersion solid-phase microextraction.
