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, (1)H and (13)C 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 (150mm×4.6mm; 5μm) using 0.02M KH2PO4 (pH=3.5) and CH3CN as a mobile phase in a gradient elution mode at a flow rate of 1.0mL/min. The eluents were monitored by PDA detector at 211nm and quantitation limits were obtained in the range of 0.1-0.3μg/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.
(Copyright © 2013 Elsevier B.V. All rights reserved.)