A simple, rapid, and robust stability-indicating RP-HPLC method has been developed and validated to measure cefixime and dicloxacillin at a single wavelength (225 nm) in order to assay. The samples were isocratically eluted using a Capcell Pak C-18 DDSS column (4.6 mm x 250 mm with a particle size of 5 mu m) with a mobile phase consisting of 5 mM phosphate buffer (with a pH adjusted to 5.4 using orthophosphoric acid): acetonitrile:methanol (42:55:03, v/v/v) delivered at a flow rate 1.0 mL min(-1). A good linear response was obtained in the range from 0.5 to 25 [kg mL-1. The LODs for CFX and CLX were found to be 0.020 and 0.018 mu g mL(-1), respectively, and the LOQs for CFX and CLX were 0.315 and 0.205 mu g mL(-1), respectively. The method was quantitatively evaluated in terms of linearity, precision, accuracy (recovery), selectivity and robustness in accordance with standard guidelines. The method is simple, convenient and suitable for analysing cefixime and dicloxacillin in bulk and in pharmaceutical formulations. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Taibah University. This is an open access article under the CC BY-NC-ND license http://creativecommons.org/licenses/by-nc-nd/4.0/