CHARACTERIZATION AND IDENTIFICATION OF TIAPRIDE HYDROCHLORIDE RELATED SUBSTANCE IMPURITIES BY UTILISING HPLC, LCMS, NMR TECHNIQUES

Abstract

Tiapride hydrochloride, an antipsychotic agent widely prescribed for the treatment of schizophrenia and various neurological disorders, was subjected to impurity profiling using advanced analytical techniques, including HPLC, LC-MS, and NMR spectroscopy. A stability-indicating LC-MS method was successfully developed and validated for the quantitative determination of tiapride in its tablet dosage form. Forced degradation studies were conducted under hydrolytic, oxidative, thermal, and photolytic stress conditions to evaluate the drug's stability. These studies led to the formation of three degradation products (DP1, DP2, and DP3), which were subsequently isolated using preparative HPLC. Structural elucidation of the impurities was performed using LC-MS, one-dimensional NMR (1H and 13C) techniques. The identified degradation products were: DP1 – N-(2- (ethylamino) ethyl)-2-methoxy-5-(methylsulfonyl) benzamide, DP2 – 2-methoxy-5- sulfonylbenzoic acid, DP3 – N-[2-(diethylnitroxyl) ethyl]-2-methoxy-5- (methylsulfonyl)benzamide (tiapride N-oxide). The validated LC-MS method exhibited excellent selectivity, specificity, accuracy, precision, and robustness for impurity detection in tiapride formulations. This comprehensive study provides critical insights into the degradation behavior of tiapride and contributes to ensuring the long-term safety and quality of both the active pharmaceutical ingredient (API) and its finished dosage forms. These findings serve as a valuable reference for future formulation development and stability studies of Tiapride-containing products.