Magnetic molecularly imprinted polymer for zearalenone in Coix: In-silico design and matrix-matched UPLC–MS/MS

Zearalenone (ZEN), a Fusarium-derived estrogenic mycotoxin, frequently contaminates Coix seeds and other grains, posing a food-safety and quality-control challenge because of the complex matrix and trace-level residue limits. Here, we developed a simulation-guided magnetic molecularly imprinted polymer (MMIP) for the rapid and selective enrichment of ZEN prior to LC–MS/MS determination. A pharmacophore model, DFT calculations, and molecular dynamics simulations were combined to identify cyclohexyl-1,4-benzenedicarboxylic acid (CDHB) as a suitable dummy template and to optimize a dual-monomer formulation (Boc-AG/MAA, ZEN: Boc-AG: MAA = 1:1:3) to strengthen complementary interactions. The resulting MMIP exhibited fast uptake (equilibrium reached in approximately 5 min), high selectivity (imprinting factor = 12.76), and a maximum adsorption capacity of 28.40 mg/g, as determined by Langmuir fitting of the equilibrium isotherms. The adsorbent also showed good reusability (≥10 adsorption–desorption cycles) with single-step desorption > 90 %. When coupled with matrix-matched LC–MS/MS, the method achieved a limit of quantification of 3.70 μg/kg and recoveries of 86.8–112.9 % for spiked Coix samples. This work demonstrates that integrating molecular simulation with magnetic imprinting enables an efficient, reusable cleanup strategy for trace ZEN monitoring in complex grain-based matrices.