Indomethacin forms by decomposition two degradation products: 4-chlorobenzoic acid and 5-methoxy-2-methylindoleacetic acid. They have to be monitored together with an active substance both during manufacturing process and storage of pharmaceuticals. European Pharmacopoeia (Ph. Eur. 4) describes titration method for determination of indomethacin, which is not very convenient in this case for practical use. Therefore, high performance liquid chromatography is the method-of-choice enabling determination of active substance and its degradation products during one-step procedure simultaneously and automatically. We have developed a fast, simple and fully automated analytical method for determination of indomethacin and its two impurities in pharmaceutical preparation using HPLC with UV detection. Various stationary phases were tested, especially new types of Zorbax columns made by Agilent. While the conventional C18 stationary phases were not convenient enough to achieve quick and reliable separation, Zorbax-Phenyl analytical column (75 mm x 4.6 mm, 3.5 microm) enables separation of indomethacin and its two degradation products during 7.5 min. Chromatography was performed using isocratic elution with binary mobile phase composed of acetonitrile and 0.2% phosphoric acid (50:50, v/v) at flow rate 0.6 ml/min. Even faster separation of standards was obtained with analytical column Zorbax SB-CN (150 mm x 4.6 mm, 5 microm). The separation was effected with mobile phase of the same composition, only the flow rate was increased to 1.2 ml/min. The analytical run was shortened to 5 min. Both methods use detection wavelength 237 nm and both can use either ketoprofen or flurbiprofen as internal standard for quantitation. The first method was finally chosen for validation because of the occurrence of placebo interferences in the case of using Zorbax SB-CN. System suitability parameters and validation parameters including method precision, accuracy, linearity, selectivity and robustness were set up. Afterwards, the method was successfully applied for the practical determination of indomethacin and its degradation products in a topical gel and for compound degradation control during stability studies.