Fluorinated‐Squaramide Covalent Organic Frameworks for High‐Performance and Interference‐Free Extraction of Synthetic Cannabinoids

Abstract Synthetic cannabinoids (SCs), one of the largest groups of new psychoactive substances (NPSs), have emerged as a significant public health threat in different regions worldwide. Analyzing SCs in water samples is critical to estimate their consumption and control. However, due to their low background concentration and the coexistence of complex matrix, the selective and effective enrichment of SCs is still challenging. In this study, a series of fluorinated‐squaramide‐based covalent organic frameworks (COF: FSQ‐2, FSQ‐3, and FSQ‐4) are synthesized, and the as‐prepared FSQ‐4 exhibits strong affinity to different SCs. The proper pore size (1.4 nm) and pre‐located functional groups (hydrogen‐bond donors, hydrogen‐bond acceptors, and fluorophilic segments) work synergistically for efficient SCs capture. Remarkably, when coupled FSQ‐4 with solid‐phase microextraction (SPME), trace‐level (part per trillion, 10 −9 ) determination of 13 SCs can be easily achieved, representing one of the best results among NPS analyses, and the excellent extraction performance can be maintained under various interfering conditions.