Pipette　tip　solid-phase　extraction　(PT-SPE)　as　a　miniaturized　solid-phase　extraction　technique　have　a　wide　range　of　applications　in　the　field　of　sample　pretreatment.　In　this　study,　ionic　covalent　organic　frameworks@cotton　(iCOF@cotton)　were　facilely　synthesized　by　mechanochemical　grinding　method　only　in　half　an　hour,　and　used　as　the　adsorbents　of　PT-SPE.　The　synthesized　iCOF@cotton　not　only　had　high　specific　surface　area,　suitable　pore　structure　and　cationic　charge　groups　of　iCOF　that　can　extract　polar　targets　quickly,　but　also　reduced　the　problem　of　high　back　pressure　of　PT-SPE　by　the　addition　of　cotton,　thus　accelerating　extraction　time.　Combined　with　high　performance　liquid　chromatographic　tandem　mass　spectrometry　(HPLC-MS/MS),　an　efficient　and　sensitive　method　was　established　for　detection　of　domoic　acid　(DA,　a　toxin　produced　by　algae).　Under　the　optimal　conditions,　the　proposed　analysis　method　displayed　excellent　analytical　performance,　including　broad　range　of　linearity　(10–1000　pg　mL−1),　low　limit　of　detection　(LOD,　5　pg　mL−1),　high　correlation　coefficient　(0.9993),　satisfactory　precision　(RSDs　≤6.4　%).　In　addition,　the　developed　method　was　applied　to　the　detection　of　DA　in　marine　samples,　and　detected　trace　DA　(18.6　pg　mL−1)　with　satisfactory　recovery　(85.7%–107.2　%).　The　above　results　indicated　that　the　prepared　iCOF@cotton　have　great　potential　as　the　adsorbents　for　PT-SPE.　©　2023　Elsevier　B.V.