Identification and characterization of forced degradation products of paliperidone using LC–APCI–Ion Trap–MS

Abstract

Degradation products of paliperidone formed under different forced conditions have been characterized through LC–UV–PDA and LC–MS studies. Paliperidone was subjected to forced degradation under the conditions of hydrolysis, oxidation, photolysis and thermal stress as prescribed by International Conference on Harmonization (ICH) guideline Q1A (R2). Three degradation products were formed and their separation was accomplished on reversed phase C-18 (4.6 × 250 mm, 5 μm) analytical column using gradient elution method. The drug degraded to products II and III under acid and alkali hydrolytic conditions while a common product I was formed under the photoacid and photoneutral conditions. No additional product was shown up under other stress conditions. Validation of the LC–DAD method was carried out in accordance with ICH guidelines. The method met all required criteria and was applied for analysis of commercially available tablets. All the products were characterized through LC–MS analyses and their fragmentation pathways were proposed. The products were proposed as 3-(1-allyl-1, 4-dihydropyridin-4-yl)-5-fluorobenzo[d] isoxazole, 5-fluoro-3-(piperidin-4-yl) benzo[d] isoxazole and 5-(2-(4-(5-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-6-methylpyrimidin-4-(3H)-one.