High-sensitivity liquid chromatography-tandem mass spectrometry quantitative for alkyl imidazolium ionic liquids in human serum: Advancing biomonitoring of human exposure concerns

Alkyl imidazolium ionic liquids (Cn[MIM]), initially heralded as eco-friendly green solvents for diverse industrial applications, have increasingly been recognized fortheir biodegradability challenges and multiple biotoxicity. Despite potential health risks, research into the effects of Cn[MIM] on human health remains scarce, particularly regarding their detection in biological serum samples. This study validated a matrix-matched calibration quantitative method that utilizes solid-phase extraction (SPE) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was used to analyze the presence of 10 ionic liquids (ILs) with varying alkyl carbon chain lengths (C₂-C₁₂) across 300 human serum samples. Efficient separation was achieved using optimized SPE conditions and a BEH C18 column with an appropriate mobile phase. Results demonstrated a strong linear relationship (0.05-100 ng/mL; R² = 0.995-0.999), with detection and quantification limits with detection and quantification limits ranging from 0.001 to 0.107 ng/mL and 0.003-0.355 ng/mL, respectively. Intraday and inter-day precisions were 0.85-6.99 % and 1.50-7.46 %, with recoveries between 82 and 113 %. The validated method detected C₆MIM in 19 % of samples and C₈MIM in 8.3 % of samples, with concentrations ranging from 0.02 to 111.70 μg/L and 0.09-16.99 μg/L, respectively, suggesting a potential risk of human exposure. This underscores the importance of robust detection methods in monitoring environmental and human health impacts of alkyl imidazolium compounds.