Surface molecularly imprinted polymer based on core-shell Fe₃O₄@MIL-101(Cr) for selective extraction of phenytoin...

Core-shell magnetic Fe₃O₄@MIL-101(Cr) nanoparticles were synthesized via layer-by-layer self-assembly method. Using Fe₃O₄@MIL-101(Cr) as support, Fe₃O₄@MIL-101(Cr)@MIP was prepared with phenytoin as template, acrylamide as functional monomer, ethylene glycol dimethacrylate as cross-linker, methanol and acetonitrile as porogen, azoisobutyronitrile as initiator. The materials were characterized by a serious of characterization experiments. The prepared Fe₃O₄@MIL-101(Cr)@MIP was demonstrated to possess good separability, large adsorption capability, excellent adsorption selectivity, good durability and reusability via adsorption experiments. Subsequently, a magnetic solid phase extraction method (MSPE) based on Fe₃O₄@MIL-101(Cr)@MIP combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) was established for the determination of phenytoin sodium in plasma samples. Experimental parameters including pH, the amount of adsorbent, extraction time, elution conditions, the concentration of NaCl were investigated to optimize extraction process. The method was validated. The linearity was observed in the range of 0.05-40 μg mL^-1 with a lower limit of quantification of 0.05 μg mL^-1. The calibration equations were y = 0.2514x + 0.0319 (r² = 0.9938), y = 0.2888x + 0.0472 (r² = 0.9943), y = 0.2565x + 0.0418 (r² = 0.9976), respectively. The recoveries ranged from 89.2 to 94.3%, intra- and inter-day precision (RSDs) ranged from 2.1 to 9.7% and 2.9-9.2%, respectively. The established MSPE-HPLC-UV method was time-saving, sensitive, accurate, environmental friendly, and drastically reduced the complex matrix interferences. The established method was successfully applied for phenytoin sodium determination in real plasma samples, providing new directions for therapeutic drug monitoring.