A new sensitive and selective electrochemical sensor was developed for determination of naltrexone (NAL) in pharmaceutical dosage form and human plasma Naltrexone is an opioid antagonist which is commonly used for the treatment of narcotic addiction and alcohol dependence. A voltammetric study of naltrexone has been carried out at the surface of glassy carbon electrode (GCE) modified with Nafion-doped carbon nanoparticles (CNPs). The electrochemical oxidation of naltrexone was investigated by cyclic and differential pulse voltammetric techniques. The dependence of peak currents and potentials on pH, concentration and the potential scan rate was investigated. The electrode characterization by electrochemical methods and atomic force microscopy (AFM) showed that CNPs enhanced the electroactive surface area and accelerated the rate of electron transfer. Application of the modified electrode resulted in a sensitivity enhancement of more than 20 times, relative to the bare GCE, in detection of NAIL and a considerable negative shift in peak potential was achieved. Two linear dynamic ranges of 1-10 mu M and 10-100 mu M with a detection limit of 0.1 mu M was obtained in phosphate buffer of pH = 3. Differential pulse voltammetry as a simple, rapid, sensitive and selective method was developed for the determination of NAL in dosage form and human plasma without any treatments No electroactive interferences were found in biological fluids from the endogenous substances and additives present in capsules (C) 2009 Elsevier B.V. All rights reserved.