Development and Validation of a Stability-Indicating UHPLC Method for Assay of Felbamate and Related Substances

A new, sensitive, stability-indicating, and cost and time-effective isocratic reversed-phase UHPLC method has been developed for quantitative analysis of felbamate, an antiepileptic drug, both in the bulk drug and in pharmaceutical dosage forms. Chromatographic separation of felbamate and its two impurities was achieved on a C(18) column with a simple buffer-methanol mobile phase; the run time was 8 min. Quantification was achieved by ultraviolet detection. Resolution between the impurities was >2.0. Response was a linear function of concentration over the range 0.1-3.0 mu g mL(-1), correlation coefficient > 0.999, for felbamate and the impurities. The method is capable of detecting the two impurities at levels of 0.002% (0.02 mu g mL(-1)) of the test concentration of 1.0 mg mL(-1) (1 mu L injection). The same sensitivity was achieved for all the degradation products formed during stress studies in which the drug was subjected to hydrolysis, oxidation, photolysis, and thermal degradation. Substantial degradation occurred under acidic and basic conditions. The stressed test solutions were assayed against felbamate working standard and the mass balance in each case was close to 100%, indicating the method is stability-indicating. The method was validated for linearity, accuracy, precision, and robustness in accordance with ICH Guidelines.