Synthesis and characterization of new surface modified magnetic nanoparticles and application for the extraction of letrozole from human plasma and analysis with HPLC-fluorescence.

ABSTRACT

Acetic acid-functionalized magnetic nanoparticles modified by (3-amino-propyl)-tri-ethoxy silane was synthesized and used as a new solid-phases adsorbent. Infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), x-ray diffraction (XRD), energy-dispersive x-ray spectroscopy (EDX), vibrating sample magnetometer (VSM) and Electrophoretic Light Scattering (ELS) were used to characterize the modified nanoparticles. The molecular interaction between letrozole and nanoparticles (NPs) was studied using density functional theory (DFT) calculations. The developed nanoparticles were applied for dispersive solid-phase extraction of letrozole (an anticancer drug) from human plasma. Extracted letrozole was quantified using an isocratic HPLC/FL method. The extraction efficiency was optimized using one experiment at a time optimization method based on the adsorbent quantity, sample pH, adsorption time, desorption time, and elution solvent type/volume. The analysis method was fully validated according to the FDA guideline for bioanalytical method validation. The linear quantification range was 0.01-1 µg/mL and the lower limit of quantification (LLOQ) was 0.01 µg/mL. Plasma samples of 6 patients were analyzed and the measured letrozole concentrations range was 0.04-0.31 µg/mL. The newly synthesized magnetic nanoparticles were used successfully for the extraction of letrozole from spiked and clinical plasma samples. The developed method is a precise and simple method that is suitable for pharmacokinetic studies and clinical applications.