Determination of 21 Kinds of Fluorinated Liquid Crystal Monomers in Human Serum by Combining Liquid-Liquid Extraction and Solid-phase Extraction with Gas Chromatography-Tandem Mass Spectrometry

An analytical method based on liquid-liquid extraction combined with solid-phase extraction (LLE-SPE) and gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed for simultaneous determination of 21 kinds of fluorinated liquid crystal monomers (FLCMs) in human serum. Quantitative internal standards were selected based on retention time and structural similarity. Instrumental conditions, extraction solvents, SPE cartridges, and elution system were systematically optimized. The optimized sample preparation procedure involved processing 250 μL of serum with concentrated sulfuric acid and methanol, followed by two sequential LLE using n-hexane and methyl tert-butyl ether. The combined extracts were concentrated under a nitrogen stream, purified on a silica gel SPE cartridge, and eluted with dichloromethane. The eluate was concentrated to near dryness with nitrogen, reconstituted in 20 μL of toluene, and analyzed by GC-MS/MS in selected reaction monitoring (SRM) mode with internal standard calibration. Method validation confirmed good linearity for the 21 kinds of FLCMs within the range of 0.5–100 μg/L (r ≥ 0.999). The method achieved limits of detection (LODs) between 0.045 and 0.272 μg/L, with limits of quantification (LOQs) ranging from 0.150 to 0.908 μg/L. The matrix effect was 86.7%–127.8%, with a mean spiked recoveries of 92.7%–134.2%. The intra-day and inter-day precisions (RSD) were 2.45%–8.62% and 2.01%–13.15%, respectively. The method was applied to 122 human serum samples, resulting in the detection of 20 kinds of FLCMs. Five of these target compounds exhibited a detection frequency greater than 50%, with median concentration range of 0.126–5.812 μg/L. This method was suitable for monitoring FLCMs in human serum from the general population, demonstrating controllable matrix effects, high accuracy, stable reproducibility, and adequate sensitivity.