The oxidative behaviour of pimozide was studied in hydroalcoholic media (10 + 90 methanol-H2O, pH range 2-7.5) at carbon based electrodes. Pimozide was irreversibly oxidized at high positive potentials, resulting in the formation of a couple with a reduction and re-oxidation peak at much lower potentials. The response was evaluated with respect to pH, scan rate, addition of surfactant and other variables. Using differential pulse voltammetry (DPV), the drug yielded a well-defined voltammetric response in Britton-Robinson buffer, pH 2.1 at + 1.1 V (versus Ag/AgCl) on glassy carbon electrode. The process could be used to determine pimozide concentrations in the range 8 x 10(-7)-1 x 10(-4) M. Applicability to tablets and human serum analysis was illustrated. Furthermore, a high-performance liquid chromatographic method with electrochemical detection (HPLC-EC) was developed, which allowed pimozide to be detected down to a level of 2.7 x 10(-10) M (0.25 ppb). (C) 2002 Elsevier Science B.V. All rights reserved.