A fast, accurate, precise and sensitive capillary electrophoresis method for the simultaneous determination of dextromethorphan hydrobromide, phenylephrine hydrochloride, paracetamol and chlorpheniramine maleate has been developed. Response surface methodology with a central composite design was used for optimization of the concentration of the buffer, pH of the buffer and applied voltage. Therefore, working with Na2HPO4 buffer (pH 8.00, 0.01 M) at 20 kV as an applied voltage in the capillary electrophoresis method were found to be suitable; under these optimal conditions, these four active ingredients were separated in about 7 min. This developed method was validated and successfully applied to a pharmaceutical preparation, sugar-coated tablet, and the results were compared with a high-performance liquid chromatographic method developed by us. 2010 © The Japan Society for Analytical Chemistry.