In the present study, a reliable LC-QTOF-MS method was developed and employed for the separation and characterization of process-related substances and forced degradation products of Lurasidone hydrochloride. The chromatographic separation was carried out using an Agilent Poroshell 120 Bonus-RP C18 column (100 mm × 4.6 mm, 2.7 µm) and a mobile phase consisting of a gradient elution of 10 mM ammonium formate solution and methanol. The degradation studies followed the guidelines outlined in ICH Q1A (R2). It was observed that Lurasidone hydrochloride exhibited instability under photolytic, alkaline, and oxidative stress conditions, while remaining relatively stable under acidic and thermal stresses. Through positive ESI-QTOF mass spectrometric analysis, fourteen related compounds in total, including both process-related and stress degradation products, were identified based on the accurate masses of parent and product ions and calculated elemental compositions. Amongst these substances, nine had not been previously reported, and their formation mechanisms were speculated. The process-related substances were further confirmed by NMR spectra determination, and suggestions were proposed to eliminate them. This study highlights the potential for monitoring and controlling related substances during the manufacturing processes, providing valuable insights for process optimization and quality control of Lurasidone hydrochloride.
Keywords: Degradation products; LC-QTOF-MS; Lurasidone hydrochloride; Related substances.
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