Electrocatalytic oxidation of penicillamine (PA) at a carbon paste electrode chemically modified with cobalt salophen as a schiff base complex (CoSal) was thoroughly investigated. The results of cyclic voltammetry (CV) and polarization studies were used for the prediction of the mechanism of electrochemical oxidation of PA mediated with CoSal at the surface of a modified electrode. The performance of the modified electrode was compared with those of electrodes modified with cobalt phthalocyanine (CoPc). In comparison, CoSal appears to be considerably more effective as a catalyst for reduction of the overpotential of the anodic oxidation of PA, resulting in a very sharp anodic CV peak at lower potentials. The results of differential pulse voltammetry (DPV) using the CoSal-modified electrode were applied in a highly sensitive determination of PA in drug and human synthetic serum samples. A linear range of 1 x 10(-4) to 1 x 10(-7) M was obtained for DPV determination of PA in buffered pH 3.0 solutions (0.1 M phosphate buffer). The modified electrode exhibits the lowest anodic overpotential ever reported for the detection of PA with modified carbon-based electrodes. The electrode has a reasonable reproducibility (RSD < 3.0%) and a very stable voltammetric response toward this compound (more than two months). (C) 2003 Elsevier B.V. All rights reserved.