RP-HPLC separation and ESI-MS, 1H, and 13C NMR characterization of forced degradants including process related impurities of carisbamate: Method development and validation

A stability indicating reversed phase HPLC method was developed and validated for determination of process related impurities and forced degradants of carisbamate (CRS) in bulk drugs. Carisbamate when subjected to acid/base hydrolysis, H2O2 oxidation, photolysis and thermal stress significant degradation was observed during acid/base hydrolysis and the degradants were isolated and characterized by ESI-MS, 1H and 13C NMR. MS/MS and 2D-NMR (COSY and HSQC) studies revealed the possible isomerization of CRS under stress conditions. The optimum separation was accomplished on Agilent XDB C18 column (150 mm × 4.6 mm; 5 μm) using 0.02 M KH2PO4 (pH = 3.5) and CH3CN as a mobile phase in a gradient elution mode at a flow rate of 1.0 mL/min. The eluents were monitored by PDA detector at 211 nm and quantitation limits were obtained in the range of 0.1–0.3 μg/mL for CRS, degradants and other impurities. The LC method was validated with respect to accuracy, precision, linearity, robustness and limits of detection and quantification as per ICH guidelines.

Chemical structure and molecular formula of carisbamate.Figure optionsDownload as PowerPoint slideHighlights
► First RP-HPLC stability indicating method for carisbamate, an anti-epileptic drug.
► First explanation to isomerization of carisbamate under acid and base hydrolysis.
► First report on McLafferty type of rearrangement in carisbamate and its isomer.
► Synthesis, isolation and characterization of carisbamate and its related substances.