A method for the separation of lidocaine and six of its metabolites in plasma has been developed. Separation was performed using a buffer consisting of 35 mM phosphate/Tris pH 3.0, 6 mM cetyltrimetylammoniumbromid (CTAB) and 9% (v/v) methanol. The key variables, CTAB and methanol concentrations, were optimized by the application of a factorial design. Rinsing the capillaries with ethanol between runs resulted in highly reproducible migration times, relative standard deviation 0.69%. Under the conditions applied, the seven analytes could be separated with high efficiency and resolution within 8.1 min. Overall performance, as demonstrated in validation experiments, was excellent. ©1999 John Wiley & Sons, Inc. J Micro Sep 11: 620–626, 1999