Synergistic integration of multi-structure recognition MIP with liquid-phase microextraction for trace analysis of synthetic cannabinoids in blood

A multi-structure recognition MIP was synthesized to target 11 synthetic cannabinoids covering six core structural classes. • An integrated MIP-LPME system was developed to overcome matrix interference in blood analysis. • Synergistic enhancement was achieved between MIP and LPME. • Ultrasensitive detection of 11 synthetic cannabinoids in blood was achieved with LOD of 2–4 ng/L. • New strategy for applying hydrophobic functional materials to complex biological matrices was proposed. Synthetic cannabinoids (SCs) pose significant challenges for forensic toxicology due to their diverse core structures and trace levels in blood. Molecularly imprinted polymers (MIPs) exhibit potential for group recognition of structurally diverse subclass of drugs, however, their direct application in blood is severely hindered by matrix interference. Conventional strategies such as sample dilution or surface modification fail to eliminate direct contact between materials and biological matrices. To address these challenges, we prepared a multi-structure recognition MIP (MR-MIP) capable of recognizing 11 SCs representing six core structural classes, and integrated it into the acceptor phase of a hollow fiber liquid-phase microextraction (HF-LPME) system. Kinetics analysis and mass distribution profiling of SCs during extraction illustrated a synergistic enhancement in which LPME protected the MIPs from blood matrix fouling while the MIPs enhanced LPME extraction efficiency through specific adsorption. The MIP-LPME system enabled simultaneous extraction of 11 SCs in whole blood, with limits of detection of 2–4 ng/L and limit of quantification of 4–10 ng/L. To the best of our knowledge, this is the first demonstration of integrating a hydrophobic MIP directly into the LPME acceptor phase for a one-step extraction, which overcomes the poor compatibility between hydrophobic functional materials and the conventional aqueous acceptor phase of LPME through tailored solvent engineering. This synergistic design not only enables highly sensitive and selective trace analysis of structurally diverse SCs in blood, but also provides a strategy for adapting LPME to hydrophobic functional materials, opening new avenues for group selective detection of diverse illicit drugs in complex biological matrices. Download: Download high-res image (152KB) Download: Download full-size image