Two novel analytical methodologies using capillary electrophoresis (CE) and liquid chromatography (LC) were developed and compared for the determination of diclofenac sodium in commercial and simulated tablet formulations. The CE analysis was performed in a bare fused-silica capillary with 75 mum id and total length of 50 cm (28 cm to the detector) with a buffer solution of 20mM sodium tetraborate, pH 9.23. The applied voltage was 20 W, and acetaminophen was used as the internal standard (IS). The LC analysis was performed with a LiChrospher((R)) 100 RP-18 (5 mum) column and a mobile phase of methanol-diluted glacial acetic acid (0.3 parts in 2500; 75 + 25) at a flow rate of 0.9 mL/min with propylparaben as the IS. In both analyses, detection was by ultraviolet absorption at 276 rim. Under optimized conditions, the CE migration times for the diclofenac sodium standard and acetaminophen (IS) were 2.07 and 1.59 min, respectively, and the LC retention times for the diclofenac sodium standard and propylparaben (IS) were 3.98 and 2.26 min, respectively. The resolution and efficiency for CE were 14.2 and 1.6 x 10(5) plates/m, respectively, and for LC, 5.0 and 8.6 x 10(3) plates/m, respectively. Calibration curves of peak area versus concentration gave correlation coefficients of 0.9992 for CE and 0.9994 for LC. The limits of detection and quantitation were 8.40 and 25.46 mug/mL, respectively, for CE and 4.60 and 13.93 mug/mL, respectively, for LC. Coefficients of variation were 1.68 and 0.37% for CE and LC, respectively. Average recoveries obtained with CE and LC were 103.12 +/- 0.90 and 99.59 +/- 0.21%, respectively. Although both methodologies were shown to be suitable for the determination of diclofenac sodium in tablets, performing in a similar manner with regard to several aspects (linearity, recovery, and specificity), CE provided faster analysis and better column efficiency, whereas LC provided superior repeatability and sensitivity.