Studies on impurities and degradation products in a potential antipsychotic agent, SIPI6398, using HPLC, semi-preparative LC, LC/ESI-MS and NMR Analyses

N-((1r,4r)-4-(2-(4-(benzo[d]isothiazol-3-yl) piperazin-1-yl)ethyl)cyclohexyl) furan-2- carboxamide hydrochloride, SIPI6398, is a potential multireceptor antipsychotic drug candidate under preclinical development. In this study, the related substances in SIPI6398 bulk substance were analyzed qualitatively and quantitatively. Specifically, its five storage degradation products (6398-YH1, 6398-YH2, 98-6-YH1, 98-6-YH2, 98-6-YH3) were isolated using semi-preparative liquid chromatography and characterized by nuclear magnetic resonance and mass spectrometry. In addition, one reversed-phase liquid chromatography method was developed for the quantification of eleven potential impurities and the main constituent, respectively. The method was validated and utilized during the impurity studies and quality control analysis during the kilogram-scale preparation of SIPI63968.