Introduction and development of smart ionic liquids (SMILs) in microextraction process: A novel methodology for the quantitative detection of THC as a biomarker of nicotine in smokers' urine and serum.

This study introduces a novel system that employs structurally analogous ionic liquids, referred to as smart ionic liquids (SMILs), for the efficient extraction and determination of trans-3'-hydroxycotinine (THC), a primary nicotine metabolite and biomarker of nicotine exposure, in urine and serum samples. Based on the molecular structure of THC, the smart ionic liquid of (S)-1-(4-hydroxypyridin-3-yl)-1-methyl-2-oxopyrrolidinium bromide ([HPOP][Br]) was rationally designed and synthesized. The key innovation of this approach lies in the specific design of the ionic liquid to enhance both selectivity and extraction efficiency. The synthesized ionic liquid was thoroughly characterized using FTIR, HNMR, CNMR, UV-Vis spectroscopy, and elemental analysis. UV-Vis spectroscopy was employed to evaluate the spectral changes associated with complex formation. Additionally, Density Functional Theory (DFT) computations were performed to elucidate the nature of the interactions and the forces governing complex formation. After extraction of THC, the resulting complex was magnetized and analyzed using vibrating sample manometer (VSM). This magnetization enabled efficient separation from the aqueous phase using a strong external magnet (NdFeB). To evaluate the accuracy, precision, and overall analytical performance of the method, key figures of merit-including the limits of detection (LOD), limits of quantification (LOQ), linear dynamic range (LDR), and inter-day and intra-day relative standard deviations (RSDs)-were determined. The obtained values (LOD: 0.12 ng/mL, LOQ: 0.25 ng/mL, LDR: 2.0-200.0 ng/mL, inter-day RSD: 2.03 %, intra-day RSD: 1.43 %) confirmed the high sensitivity, precision and reliability of the method. Finally, the developed method was applied to real urine samples obtained from both smokers and non-smokers, as well as to real water samples with containing complex matrices. The method successfully quantified THC in all real samples with an accuracy ranging from 95.4 to 98.8 %.