Ionic-liquid-based extraction strategies for the analysis of bioactive constituents in traditional Chinese medicines: applications, advances, and challenges.

Traditional Chinese Medicine (TCM) exerts its therapeutic effects through multiple bioactive constituents acting on multiple targets, while the analysis of trace-level compounds in complex herbal matrices remains challenging for quality control. Conventional extraction procedures may require substantial amounts of volatile organic solvents and prolonged treatment, motivating the development of more efficient and miniaturized sample-preparation strategies. Ionic liquids (ILs), characterized by negligible vapor pressure and tunable physicochemical properties, have therefore attracted considerable interest as designer extraction media. This review critically summarizes recent advances in ionic-liquid-based extraction and microextraction for the analysis of bioactive constituents in TCM. Phase-based liquid-phase microextraction formats, including ionic liquid-based dispersive liquid-liquid microextraction (IL-DLLME), homogeneous liquid-liquid microextraction (IL-HLLME), aqueous biphasic systems (IL-ABS), single-drop microextraction (IL-SDME), and supported or membrane-based LPME, are distinguished from energy-assisted solid-liquid extraction strategies such as ionic liquid-based ultrasound-assisted extraction (IL-UAE) and microwave-assisted extraction (IL-MAE). Ionic-liquid-modified solid-phase and magnetic solid-phase extraction, as well as hybrid and multiphase configurations, are also discussed. Representative TCM applications are organized according to extraction methodology rather than analyte class, with emphasis on the relationships among IL structure, extraction mechanism, analyte properties, selectivity, and multi-component coverage. The coupling of IL-based extraction with chromatographic, mass-spectrometric, spectroscopic, and capillary-electrophoretic techniques is further examined. Current challenges, including viscosity, potential toxicity, IL recovery, instrumental compatibility, reproducibility, and scale-up, are critically evaluated together with future opportunities involving task-specific ILs, magnetic and polymeric IL materials, and data-driven solvent design.