Ultrasound assisted dispersive micro solid-phase extraction of four tyrosine kinase inhibitors from serum and cerebrospinal fluid by using magnetic nanoparticles coated with nickel-doped silica as an adsorbent

Nanoparticles (NPs) consisting of a magnetic Fe₃O₄ core and a nickel(II)-doped silica shell were prepared and are shown to be viable materials for selective magnetic extraction of trace quantities of the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, erlotinib and sunitinib. The NPs were characterized by scanning electron microscopy, transmission electron microscopy, DLS and XRD analysis, and the results revealed a uniform in size (with a typical diameter of 40 nm) and a core-shell structure. The magnetic nanoadsorbent displays good affinity of the TKIs, probably because of the affinity between the Ni(II) ions of the NPs with the nitrogen atoms in the TKIs. The magnetism of the NPs enables them to be quickly separated from serum and cerebrospinal fluid samples. Imidazole, with its higher affinity for Ni(II) than that of the TKIs, was used for desorption of the TKIs from the NPs prior to their quantification by HPLC with UV detection. The detection limits are as low as 200, 480, 130, and 250 ng·L￣¹ for imatinib, sunitinib, erlotinib, and nilotinib, respectively. The intra-day precisions (RSDs) were lower than 4.0 %. The method displays a wide linear range. It was applied to the determination of TKIs in (spiked) human serum and cerebrospinal fluid and gave recoveries in the range from 94.6 to 98.6 %.