A novel micro-extraction procedure was developed through the use of an electrospun polymer nanofiber as a solid-phase extraction (SPE) sorbent to directly extract trazodone from human plasma. The target compound was then monitored by a high performance liquid chromatography with ultraviolet detector (HPLC-UV) system. Parameters of influencing the extraction efficiency, such as fiber diameter, fiber packing amount, eluted solvent, pH and ionic strength were investigated. Under the optimized conditions, a linear response for trazodone over the range of 20-2000 ng mL(-1) was achieved with a gamma(2) value of 0.9996. The precision of the method was examined with relative standard deviations of 5.7, 2.7, 2.2% corresponding to 50, 200, and 500 ng mL(-1), respectively, of trazodone spiked into 0.1 mL of plasma samples. The extraction recoveries of 58.3-75.2% and the relative recoveries of 94.6-105.5% were obtained. The limit of detection (LOD) was determined to be 8 ng mL(-1). A 15 min of HPLC gradient was successfully applied to determine trazodone from human plasma. Due to its simplicity, selectivity and sensitivity, the method may be applied to pharmacokinefic and pharmacodynamic studies of drugs. (c) 2007 Elsevier B.V. All rights reserved.