Abstract: In this study, conventional thin-film microextraction (TFME) was endowed with magnetic by intro-ducing superparamagnetic SiO2@Fe3O4nanoparticles in thin-films. Novel magnetic octadecylsilane(ODS)-polyacrylonitrile (PAN) thin-films were prepared by spraying, and used for the microextrac-tion of quetiapine and clozapine in plasma and urine samples, followed by the detection of HPLC-UV.The influencing factors on the extraction efficiency of magnetic ODS-PAN TFME, including pH, extrac-tion time, desorption solvent, desorption time, and ion strength were investigated systematically.Under the optimal conditions, both analytes showed good linearity over ranges of 0.070–9.000 g mL−1and 0.012–9.000 g mL−1in plasma and urine samples, respectively, with correlation coefficients (R2)above 0.9990. Limits of detection (LODs) for quetiapine in plasma and urine samples were 0.013and 0.003 g mL−1, respectively. LODs for clozapine in plasma and urine samples were 0.015 and0.003 g mL−1, respectively. The relative standard deviations (RSDs) for quetiapine and clozapine wereless than 9.23%. After the validation, the protocol was successfully applied for the determination of queti-apine and clozapine in patients’ plasma and urine samples with satisfactory recoveries between 99–110%.The proposed magnetic ODS-PAN TFME was very simple, fast and easy to handle. It showed high poten-tial as a powerful pretreatment technology for routine therapeutic drug monitoring (TDM) in plasma andurine samples.