Stress degradation studies on Lafutidine: method development and characterization of degradation products using HPLC-UV and LC-ESI-MS

Abstract Background Forced degradation studies are performed to understand stability, develop analytical methods, identify degradation products, establish degradation pathways, and generate more stable formulations. The objective of this work was to study the degradation behavior of the Lafutidine as per ICH-recommended conditions, to identify the degradation products, and to suggest the most probable mechanism of formation of degradation products using LC and LC-MS/MS. Methods Lafutidine was subjected to different ICH-recommended stress conditions like oxidation, thermal stress, photolysis, and hydrolysis in acidic, alkaline, and neutral medium. The degradation products were well separated on a Hypersil BDS C18 column by isocratic elution mode. Mobile phase was methanol and (0.05 M) ammonium acetate buffer, 45:55 (v/v), at a flow rate of 1.8 mL/min at 273 nm. The degradation products were subjected to LC-ESI-MS studies without separation of them from the stressed samples. Out of seven, the most likely structures of six nonvolatile degradation products (degradation product A–degradation product F) were identified and the chemical structures were proposed based on the data obtained in the mass spectral studies. Results The structures of six degradation products were suggested to be: 2-((furan-2-yl)methylsulfinyl- N -((E)-4-hydroxybut-2-enyl)acetamide—degradation product A, 2-((furan-2-yl)methylsulfinyl-N-((E)-4-methoxybut-2-enyl)acetamide—degradation product B, 2-((furan-2-yl)methylsulfinyl)acetamide—degradation product C, (E)-4-(4-((piperidin-1-yl)methyl)pyridine-2-yloxy)but-2-en-1-amine—degradation product D, N -((E)-4-(4-((piperidin-1-yl)methyl)pyridine-2-yloxy)but-2-enylacetamide—degradation product E, and 2-((E)-5-(furan-2-yl)methylsulfinyl)pent-2-enyloxy-4-((piperidin-1-yl)methylpyridine—degradation product F. Conclusion The stress degradation analysis was performed on Lafutidine. The drug was found to degrade more readily in alkaline environment, less readily in acidic, oxidative, and photolytic environments and quiet stable under and neutral conditions. Since the method could separate the all degradation products from Lafutidine, the method was concluded to be stability-indicating one. For the first time, the authors are reporting new degradation products formed under alkaline and photolytic conditions. Most probable mechanisms for the formation of the degradants are also proposed.