title: RP-HPLC separation and ESI-MS, 1H, and 13C NMR characterization of forced degradants including process related impurities of carisbamate: method development and validation.
abstract: 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.
authors: Analytical Chemistry Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India. rnrao@iict.res.in
authors: Ramisetti Nageswara
authors: RN
authors: Rao
authors: Kuntamukkala
authors: K
authors: Ramakrishna
authors: Bompelli
authors: B
authors: Sravan
authors: Kondapalli
authors: K
authors: Santhakumar
mesh_terms: D002219:Carbamates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010782:Photolysis; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; D006861:Hydrogen Peroxide