In this research, a novel carbon nanoparticles (Emperor 2000 (TM))-modified carbon paste electrode (CNP/CPE) was fabricated and employed for determination of paracetamol (PA), phenylephrine (PHE) and dextromethorphan (DX) with good selectivity and high sensitivity. The paste design is based on (i) a hydrophobic binder, (ii) hydrophobic graphite as conductive component, and (iii) a thin film of nanoparticulate with hydrophilic surface to provide sensitivity and selectivity. Paracetamol, phenylephrine and dextromethorphan are frequently associated in pharmaceutical formulations against the common cold. Then determination of these compounds in a mixture is very important in pharmaceuticals and human fluids. CNP/CPE displayed excellent electrochemical catalytic activities towards paracetamol, phenylephrine and dextromethorphan oxidation. Using differential pulse voltammetry (DPV), a trace determination of PA, PHE and DX has been explored at the surface of modified electrode in presence of each other. Peak currents of PA, PHE and DX increased linearly with their concentrations at the ranges of 1.0 x 10(-7)-1.0 x 10(-3) M, 8.0 x 10(-6)-8.0 x 10(-5) M and 8.0 x 10(-6)-8.0 x 10(-4)M, and the detection limits were estimated 1.5 x 10(-8), 9.5 x 10(-7) and 2.9 x 10(-6)M, respectively. The modified electrode displayed strong function for resolving the overlapping voltammetric responses of PHE and DX into two well-defined voltammetric peaks. Method was applied successfully to the determination of PA, PHE and DX in real samples. (C) 2014 Elsevier B.V. All rights reserved.