Magnetic solid phase extraction followed by in-situ derivatization with core-shell structured titanium dioxide coated...

In this study, for the first time, magnetic solid phase extraction (MSPE) was combined with in-situ derivatization to determine alendronate in plasma. TiO₂ coated Fe₃O₄ microspheres (denoted as Fe₃O₄@TiO₂) were synthesized via polydopamine coating, titanium ions immobilizing and calcination steps. The as-prepared microspheres could selectively extract alendronate and be quickly isolated from plasma. The drug-adsorbed Fe₃O₄@TiO₂ microspheres were then directly incubated in derivatization reagent solution to perform novel in-situ derivatization and elution procedure, in which the derivatized alendronate lost its affinity to TiO₂ and was spontaneously eluted for further LC-MS/MS detection. Satisfactory results were obtained on the creative attempt to couple dispersive magnetic solid phase extraction with in-situ derivatization. The developed method was validated and demonstrated good linearity (0.05-500 ng mL^-1), low detection limit (20 pg mL^-1), great accuracy (100.6% to 105.3%) and precision (RSDs<5.27%). Manual operation and analysis time could be greatly reduced compared to other reported methods. The method was successfully applied to a pharmacokinetic study in beagle dogs.