Structural elucidation of two novel degradants of lurasidone and their formation mechanisms under free radical‐mediated oxidative and photolytic conditions via liquid chromatography‐photodiode array/ultraviolet‐tandem mass spectrometry and one‐dimensional/two‐dimensional nuclear magnetic resonance spectroscopy

Lurasidone is an antipsychotic drug clinically used for the treatment of schizophrenia and bipolar disorder. During a mechanism‐based forced degradation study of lurasidone, two novel degradation products were observed under free radical‐mediated oxidative (via AIBN) and solution photolytic conditions. The structures of the two novel degradants were identified through an approach combining HPLC, LC‐MSn (n = 1, 2), preparative HPLC purification and NMR spectroscopy. The degradant formed under the free radical‐mediated condition is an oxidative degradant with half of the piperazine ring cleaved to form two formamides; a mechanism is proposed for the formation of the novel N,N′‐diformyl degradant, which should be readily applicable to other drugs that contain a piperazine moiety that is widely present in drug molecules. The degradant observed under the solution photolytic condition is identified as the photo‐induced isomer of lurasidone with the benzisothiazole ring altered into a benzothiazole ring. [ABSTRACT FROM AUTHOR]