An optimized capillary zone electrophoresis (CZE) method for the analysis of tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC) and doxycycline (DXC) is described. Using fused-silica capillaries, the influence of the electrolyte composition, pH and concentration, as well as temperature and applied voltage were investigated. A factorial and central composite design was performed to optimize the method in a simple way. The optimal separation conditions were 50 mmol L-1 sodium carbonate + 1 mmol L-1 EDTA, pH 10; voltage 13 kV and temperature 23 degrees C. The method was validated for TC determination in pharmaceuticals through the following performance criteria: linearity and linear range, sensitivity, selectivity, intra-assay and inter-assay precision, detectability, accuracy and ruggedness. In comparison with the recommended HPLC method in the United States Pharmacopeia, this CZE-method exhibited the same performance as the official method, with the advantage that the same method could be used for the simultaneous determination of the different tetracyclines in pharmaceutical formulations. (c) 2006 Elsevier B.V. All rights reserved.702236243