Identification and characterization of stress degradants of lacosamide by LC–MS and ESI-Q-TOF-MS/MS: Development and validation of a stability indicating RP-HPLC method

• First explanation to isomerization of lacosamide under base hydrolysis.
• Six degradants were characterized by ESI-MS/MS & accurate mass measurements.
• First report on characterization of lacosamide isomeric degradant by MS/MS and NMR.
• RP-HPLC stability indicating method for lacosamide and its related substances.

The current study dealt with the degradation behavior of lacosamide (LAC) under ICH prescribed stress conditions. LAC was found to be labile under acid and base hydrolytic stress conditions, while it was stable to neutral hydrolytic, oxidative, photolytic and thermal stress. In total, seven degradation products (DPs) were formed, which were separated on a C18 column using a stability-indicating method. LC–MS analyses indicated that one of the DPs had the same molecular mass as that of the drug. Structural characterization of DPs was carried out using ESI-Q-TOF-MS/MS technique. The degradation pathways and mechanisms of degradation of the drug were delineated by carrying out the degradation in different co-solvents viz. methanol, deuterated methanol, ethanol, 1-propanol and acetonitrile. The developed LC method was validated for the determination of related substances and assay of LAC as per ICH guidelines. This study demonstrates a comprehensive approach of LAC degradation studies during its development phase.

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