Abstract: AimTo develop a rapid and feasible method based on micellar electrokinetic capillary chromatography (MECC) for the simultaneous determination of antiepileptic drugs (AEDs)phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), primidone (PRM) and clonazepam (CZP) in human plasma. MethodsSeveral factors that impact the separation of AEDs with MECC were investigated, such as concentration of sodium dodecyl sulfate (SDS), buffer compositions, pH, organic modifier, internal diameter and temperature, and an optimized MECC running condition was obtained the running buffer consisted of 8 mmol·L^-1 phosphate, 3 mmol·L^-1 sodium tetraborate, and 50 mmol·L^-1 sodium dodecylsulfate (SDS) (pH 8.0), containing acetonitrile (ACN) (18%) as organic modifier. Detection at 210 nm, run at 25 kV at 30 ℃ in a untreated fused silica capillary (50/45.5 cm length, 50 μm ID). ResultsThe reproducibility of both migration time and relative peak area with MECC analysis were appropriate for the intra- and inter-assay coefficients. The evaluated drugs concentration intervals of PRM 1.0-40.0 μg·mL^-1, PB 1.0-60.0 μg·mL^-1, PHT 1.0-40.0 μg·mL^-1, CBZ 1.0-40.0 μg·mL^-1, CZP 0.2-8.0 μg·mL^-1 were linear with correlation coefficients higher than 0.999 1, and coefficients of the variation of the points of the calibration curve lower than 10%. The recoveries of AEDs varied from 80.0% to 100.0%, depending on the drug, with coefficients of the variation lower than 10.0%. ConclusionThe MECC technique is showed to be rapid, simple, efficient and low cost when applied to monitoring therapeutic drugs in patient treated with a combination of PHT and other AEDs such as hepatic enzyme-inducing agents.