Facile synthesis of Cu²⁺-immobilized magnetic covalent organic frameworks for highly efficient enrichment and sensitive determination of five phthalate monoesters from mouse plasma with HPLC-MS/MS

Development of a simple, highly selective, and sensitive analytical method for phthalate monoesters (mPAEs) remains a challenge due to the complexity of biological samples. To address this issue, Cu²⁺ immobilized magnetic covalent organic frameworks (Fe₃O₄@TtDt@Cu²⁺ composites) with core-shell structures were prepared to enhance the enrichment efficiency of mPAEs by a facile approach synthesis of COFs shells with inherent bifunctional groups on Fe₃O₄ NPs and further Cu²⁺ immobilization. The composites exhibit high specific surface area (348.1 m² g⁻¹), outstanding saturation magnetization (34.94 emu g⁻¹), ordered mesoporous structure, Cu²⁺ immobilization, and excellent thermal stability. Accordingly, a magnetic solid-phase extraction (MSPE) pretreatment technique based on Cu²⁺ immobilized COF composites combined with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established, and key parameters including the adsorbent amount, adsorption time, elution solvent, etc. were examined in detail. The developed analytical method showed wide linear ranges (10–8000 ng L⁻¹), low limit of detections (LODs, 2–10 ng L⁻¹), and good correlation coefficients (R² ≥ 0.9904) for the five mPAEs. Furthermore, the analytical method was also successfully applied to the highly sensitive detection of metabolite mPAEs in mouse plasma samples, indicating the promising application of the Fe₃O₄@TtDt@Cu²⁺ composites as a quick and efficient adsorbent in the sample pretreatment.