Two novels simple, accurate, sensitive and reproduciblemethods have been developed and subsequently validated for the determination of itopride Hydrochloride in presence of its acidic and oxidative-degradates, as stability- indicating studies. In the first method, zero-crossing technique was adopted for determination of the investigated drug in presence of its acidic and oxidative-degradates, by the use of derivative and derivative ratio spectrophotometry, respectively. The second method was based on isocratic high-performance liquid chromatography (HPLC) separation of itopride Hydrochloride from its acidic and oxidative-degradates on a reversed phase ODS columns, utilizing (methanol: phosphate buffer at pH= 4.0) (35:65, v/v) as a mobile phase. The flow rate was 1.0 ml.min-1 and the samples were detected by using UV detector at 258 nm and fluorescence detector 291/ 342nmas excitation/emission wavelengths.All the proposed methods were validated according to the International Conference onHarmonization (ICH) guidelines and successfully applied for determination of the itopride Hydrochloride in pure form, in laboratory preparedmixtures and in pharmaceutical preparations. The obtained results were statistically compared to the manufacturerÂs method of analysis for itopride Hydrochloride and no significant differences were found.