In this study, pK(a) values were determined by using the dependence of the capacity factor on the pH of the mobile phase for four ionizable substances, namely, tenoxicam, piroxicam, meloxicam, and naproxen (I.S.). The effect of the mobile phase composition on the ionization constant was studied by measuring the pK(a) at different ACN concentrations, ranging from 30 to 40%. The adequate condition for the chromatographic determination of these compounds in pharmaceutical dosage forms was established based on the different retention behaviors of the species. An octadecylsilica Nucleosil C18 column (150 x 4.6 mm, 5 microm) was used for all the determinations. The chromatographic separation of oxicams was carried out using acetonitrile (ACN)/water at 35% v/v, containing 65 mM phosphoric acid and UV detection at a wavelength of 355 nm. The method developed was successfully applied to the simultaneous determination of these drug compounds in laboratory-prepared mixtures and their commercial pharmaceutical dosage forms. Each analysis requires no longer than 12 min.