Surface-Enhanced Raman Spectroscopy for Propofol Detection in Postoperative Patient Whole Blood Samples

Propofol remains the first sedative choice due to its rapid onset and short distribution half-life. However, the narrow therapeutic window and pronounced inter-individual pharmacokinetic variability pose challenges in achieving appropriate sedation levels in diverse patients, calling for rapid and accurate quantification of propofol for its clinical safety. In this work, a sensitive and rapid surface-enhanced Raman scattering (SERS) platform based on vertically aligned Au nanorods array with enhancement factor >10⁷ was fabricated for directly propofol detection in unprocessed postoperative blood samples. Achieving by rapid and selective derivatization of propofol with 2,6-dichloroquinone-4-chloroimide (DCQ) in alkaline conditions, the SERS platform presented excellent selectivity resulted by a strong 1278 cm^-1 peak of indophenol. This assay displayed a linear response from 1 ng mL^-1 to 20 µg mL^-1 with a limit of detection of 0.38 ng mL^-1 in 2 min for each sample. Both the artificial simulated serum and clinical postoperative blood samples testing demonstrated excellent quantification performance of as-prepared SERS platform. Significantly, Comparative analysis with high-performance liquid chromatography (HPLC) showed a Deming slope of 0.95, confirming analytical interchangeability. Moreover, A subsequent cohort of 32 patients demonstrated a robust inverse correlation between SERS-derived propofol levels and Richmond Agitation-Sedation Scale scores (Spearman ρ=-0.80, p<0.0001), a single threshold of 1.17 µg mL^-1 predicted moderate sedation to deep sedation with 100% sensitivity and 100% specificity. This work furnishes the first clinically validated, reagent less-cleanup SERS assay for intravenous anesthetic monitoring, offering a generic blueprint for real-time therapeutic-drug management in critical care.