Abstract: A novel and sensitive analytical method was developed for the rapid detection of five fluoroquinolone (FQ) antibiotics in honey, utilizing solid-phase extraction (SPE) based on a phosphonate functionalized covalent organic framework (COF-Tb-TBBP) in conjunction with high-performance liquid chromatography (HPLC). The COF-Tb-TBBP material was synthesized via a solvothermal method, followed by comprehensive characterization of its morphological features and surface chemistry. Key parameters affecting extraction efficiency, such as adsorbent dosage, adsorption time, desorption solvent and desorption solvent dosage, were optimized via comprehensive evaluations. Experimental evaluations revealed that the COF-Tb-TBBP exhibited an exceptionally high surface area and abundant phosphonate binding sites, facilitating rapid and selective interactions with FQ molecules. Optimal extraction conditions were established as follows: 10 mg of adsorbent, a 3-min adsorption period, and elution with 2 mL of 5% formic acid in acetonitrile. Under these conditions, the method achieved detection limits as low as 0.002~0.003 mg/kg and yielded spiked recoveries ranging from 92.52% to 98.95%. These results underscore the method's effectiveness for trace-level quantification of FQs in honey. Overall, the SPE-HPLC platform based on COF-Tb-TBBP offers a robust, efficient, and practical solution for the monitoring of antibiotic residues in food safety applications.