Two RP-LC methods have been developed for the simultaneous determination of ibuprofen (IBU) and two skeletal muscle relaxants, namely methocarbamol (MET) or chlorzoxazone (CHZ), in the presence of their degradation products. In the first method, the simultaneous determination of IBU and MET in the presence of guaifenesin (GUF), a degradation product of MET, was developed. Chromatographic separation was achieved on an Inertsil CN-3 column (250 mm x 4.6 mm, 5 mu m). Gradient elution based on 0.5% aqueous phosphoric acid (pH 2.8) - acetonitrile at a flow rate of 1 mL min(-1) was applied with UV detection at 229 nm for IBU and 274 nm for MET and GUF. Linearity, accuracy, and precision were found to be acceptable over the concentration ranges of 5-160 mu g mL(-1) for IBU and 2.5-160 mu g mL(-1) for MET and GUF. In the second method, the simultaneous determination of IBU and CHZ in the presence of CHZ degradation product, 2-amino-4-chlorophenol (CDE), was developed. In this method, chromatographic separation was achieved on Reprosil-Pur C-8 (250 mm x 4.6 mm, 5 mu m). A gradient mobile phase system consisting of acetonitrile and 0.2% aqueous triethylamine (pH 5.1) at a flow rate of 1 mL min(-1) was applied with UV detection at 229 nm for the three compounds. Linearity, accuracy, and precision were found to be acceptable over the concentration ranges of 2.5-250 mu g mL(-1) IBU and CHZ, and 2.5-150 mu g mL(-1) CDE. The optimized methods were validated and proved to be specific, robust, and accurate for the quality control of the cited drugs in synthetic mixtures and pharmaceutical preparations.