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 absorb ing degradation product, Ro 5-5172, in clidinium bromide drug substanc e. The electrophoresis buffer consisted of sodium phosphale and benzyl trimethylammonium bromide. Rinsing the capillary with sodium hydroxide followed by water then fresh capillary electrophoresis buffer was fou nd to significantly improve the reproducibility of the migration times of the analytes. To further improve run-to-run reproducibility, an in ternal marker was used to account for differences in injection volumes and migration times between runs. The precision of the method was fou nd to be less than 1% relative standard deviation for the migration ti me ratio and peak area ratio of Ro 5-5172 to the internal standard. Th e 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 l ayer chromatography method were compared and found to be in agreement. (C) 1997 Elsevier Science B.V.