A novel extraction technique was reported. The solid phase material, nanofiber, was prepared by electrospinning using polystyrene. Twenty different drugs (10 mu g/L in water) were extracted using 1 mg of nanofibers within 5 min. The analytes can be desorpted from the fibers with 50 mu L of the methanol and then monitored by LC coupled to a UV detector. Packed-fiber SPE (PFSPE) provide high recoveries (>50%) for non-polar drugs (log P >1.5) (n-octanol-to-water partition ratio), and some relatively relatively low recoveries (9.9-39.8%) for the drugs within the log P window below 1. Experimental optimization of the technique has been carried out using seven representative drugs, edaravone, cinchonine, quinine, voriconazole, chlordiazepoxide, verapamil, and rutonding. Except for edaravone, the maximum yields of seven drugs (0.2 mu g/L) from water samples were approximately 100%, and were 33.7-88.2% from human plasma. The advantageous aspect of the technique encompasses high throughput, high sensitivity, simplicity, low cost, and green chemistry.