Development of a Validated Stability Indicating LC Method for Lamotrigine

The present method provides the detailed description of development of a simple, time efficient stability indicating reversed phase column liquid chromatographic method for lamotrigine in the presence of its impurities namely Imp-A, Imp-B, Imp-C, Imp-D, Imp-E, Imp-F and degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of aqueous hydrolysis, oxidative, photolytic and thermal stress degradation. The degradation of lamotrigine was observed under acid hydrolysis, base hydrolysis and peroxide. The drug was found to be stable to other stress conditions attempted. Successful separation of the drug from the synthetic impurities and degradation product formed under stress conditions was achieved on Symmetry C18, 75 mm × 4.6 mm column using aqueous trifluoroacetic acid and acetonitrile. The developed LC method was validated with respect to linearity, accuracy, precision, specificity and robustness. The assay method was found linear in the range of 5–60 μg mL−1 with correlation coefficient of 0.9999 and the linearity of the impurities were established from LOQ to 0.2%. Recoveries of assay and impurities were found between 99.1 and 101.4%. The developed LC method to determine the related substances and assay determination of lamotrigine can be used to evaluate the quality of regular production samples and stability samples. To the best of our knowledge, the validated stability indicating LC method which separates all the impurities disclosed in this investigation was not published elsewhere.