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

Abstract 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.