With　the　increase　of　alternative　per-　and　polyfluoroalkyl　substances　(PFASs)　across　various　applications,　the　environmental　and　toxicological　implications　are　emerging　as　critical　issues　of　increasing　scientific　and　public　concern.　Accordingly,　analytical　methodologies　must　be　enhanced　to　accurately　detect　and　evaluate　these　alternative　PFASs.　Herein,　a　cationic　guanidine-based　covalent　organic　frameworks　(TG-BPY　COF)　was　synthesized　via　a　one-step　solvothermal　method　for　the　efficient　extraction　of　alternative　PFASs.　TG-BPY　COF　demonstrated　good　chemical　stability　and　reusability.　It　possessed　a　specific　surface　area　of　184.66　m2/g　and　exhibited　an　adsorption　capacity　of　185.24,　182.41,　160.97,　160.56,　and　232.03　mg　g−1　toward　PFBA,　PFBS,　PFHxA,　PFHxS,　and　6:2　Cl-PFESA,　respectively.　The　characterization　and　density　functional　theory　(DFT)　calculation　revealed　that　the　binding　mechanism　between　the　TG-BPY　COF　and　alternative　PFASs　involves　size　effects,　hydrophobic　interactions,　and　electrostatic　interactions.　Under　optimal　conditions,　a　simple　and　highly　sensitive　method　was　established　for　the　quantitative　analysis　of　five　alternative　PFASs　by　combining　dispersive　solid-phase　extraction　with　ultrahigh-performance　liquid　chromatography-tandem　mass　spectrometry　(dSPE-UPLC-MS/MS).　The　established　methods　demonstrated　excellent　linearity　with　the　alternative　PFASs　concentration　range　of　0.10　to　500　ng　L−1　(r　≥　0.9997),　along　with　extremely　low　limits　of　detection　(0.030–0.044　ng　L−1),　and　high　enrichment　factors　(16.2–61.4).　Furthermore,　the　method　was　applied　to　detect　trace-level　alternative　PFASs　in　environmental　water　samples,　and　satisfactory　recoveries　(78.7　%–122.8　%)　and　relative　standard　deviations　(RSDs　≤8.7　%)　were　achieved.　This　work　not　only　provides　an　application　scope　for　cationic　covalent　organic　frameworks,　but　also　offers　a　new　strategy　for　the　extraction　of　alternative　PFASs　in　wastewater.　©　2025　Elsevier　B.V.