The determination of a degradation product in clidinium bromide drug substance by capillary electrophoresis with indirect UV detection.

A capillary electrophoresis (CE) method utilizing indirect ultraviolet (UV) detection was developed for the determination of a non-UV absorbing degradation product, Ro 5-5172, in clidinium bromide drug substance. The electrophoresis buffer consisted of sodium phosphate and benzyltrimethylammonium bromide. Rinsing the capillary with sodium hydroxide followed by water then fresh capillary electrophoresis buffer was found to significantly improve the reproducibility of the migration times of the analytes. To further improve run-to-run reproducibility, an internal marker was used to account for differences in injection volumes and migration times between runs. The precision of the method was found to be less than 1% relative standard deviation for the migration time ratio and peak area ratio of Ro 5-5172 to the internal standard. The method was found to be linear for 0.05-1% Ro 5-5172 with respect to a 10 mg ml-1 sample preparation. The limit of detection was found to be less than 0.01% Ro 5-5172. Results obtained for the analysis of a clidinium bromide drug substance lot using this CE method and a thin layer chromatography method were compared and found to be in agreement.