The purpose of this study was to assess the possibility of using ultrafiltration-based extraction for pharmaceutical analysis and develop an innovative, rapid and simple analysis technique for determination of naproxen sodium in human plasma. The proposed extraction technique can be adapted for wide range of active pharmaceutical ingredients including water-soluble nonsteroidal anti-inflammatory drugs. Naproxen sodium was isolated from human plasma by ultrafiltration-based extraction and analyzed by HPLC. Proteins in the plasma samples were precipitated with methanol and the supernatant was filtered through commercial centrifugal filters (< 3 kDa). The filtered part was vacuum centrifuged, dried, and then dissolved in water and centrifuged again. The supernatant was injected into the HPLC system where an ACE 5 mu m C18 100 LC column (150 x 4.6 mm) was used. The mobile phase was acetonitrile - phosphate buffer (pH 3.0, 20 mM) 55 : 45 v/v mixture, the injection volume was 20 mu L, and the UV detection was performed at 240 nm. Using the developed extraction technique combined with HPLC method, plasma samples containing naproxen sodium were successfully analyzed (RSD 1.04-6.47, bias 2.33-6.00).