A hydrophobic surface modified iron oxide magnetic nano-sorbent was successfully synthesized, characterized and utilized for highly effective removal and recovery of Berberine (Brb) by Ultrasound Assisted Dispersive Magnetic Solid Phase Extraction (UADM-SPE). Fabrication of p-Naphtholbenzein-coated magnetic nanoparticles (PNB-MNPs) was certified by characteristic analyses such as: Fourier transform infrared spectroscopy (FT-IR), X-ray Diffraction (XRD), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The characterized PNB-MNPs were utilized to develop a UADM-SPE method for Brb, a wellknown isoquinoline alkaloid with a highlighted chemical skeleton for designing selective and powerful bioactive molecules. Affecting parameters on the extraction of Brb were optimized through an orthogonal rotatable central composite design (CCD). The optimum condition is obtained when the variables are set to: pH¼4, amount of MNPs¼20 mg, sample volume¼30 ml, sonication time¼1 min at room temperature, and desorbing solvent¼500 mL of methanol. Under the mentioned condition, an extraction recovery of 98.2%, with relative standard deviation of 3.7%, was obtained via five replicated measurements on a 0.1 mg L1 Brb standard solution. Finally, the method was successfully applied for determination of Brb in human plasma and urine samples. Regarding the method calibration graphs in plasma and urine matrices, spiked in the range of 0.01–200.00 mg L1, pre-concentration factors of 134 and 122, method detection limit (MDL) of 0.17 and 0.19 mg L1, and lower limit of quantification of 0.57 and 0.63 mg L1 were obtained for plasma and urine samples, respectively. The method exhibits good potentials to be a fast, efficient and reliable method for determination of Brb in human biological samples
