Development and validation of a capillary electrophoresis method for ximelagatran assay and related substance determination in drug substance and tablets.

The advantages of simplicity, selectivity, versatility and ease of use of free solution capillary electrophoresis (CE) present an orthogonal and complementary separation technique to the established methods of liquid chromatography (LC) for pharmaceutical analysis. This work presents the development and performance of a suitable CE method for ximelagatran (formerly H 376/95) assay and related substance determination in both drug substance and tablets. The method employed was a low pH phosphate buffer, to which acetonitrile and hydroxypropyl-beta-cyclodextrin were added, in order to facilitate the separation of ximelagatran and its related substances. An applied field of 350 V/cm was used and all compounds were resolved in approximately 20 min. Benzamidine hydrochloride was used as an internal standard in quantification. The data indicate that the performance of the validated method offers equivalent and complementary information, in terms of selectivity, sensitivity, accuracy, linearity and precision, to that of an established gradient LC method employed for similar purposes. Robustness of the method was investigated by experimental design and evaluated using multivariate calculations.