THE SEPARATION OF IPRATROPIUM BROMIDE AND ITS RELATED-COMPOUNDS

Ipratropium bromide, the active component in ipratropium bromide meter ed dose inhalers (MDI), is used as a bronchodilator for the maintenanc e and treatment of bronchospasms associated with chronic obstructive p ulmonary disease (COPD). The separation of ipratropium bromide, tropic acid, N-isopropyl-nor-atropine (NINA), 8-s ipratropium bromide, apo-i pratropium bromide and the excipients found in the formulation is impo rtant for analyzing raw materials and stability samples. We now report a reversed-phase HPLC method that can be used for separating ipratrop ium bromide and its related compounds, using an acetonitrile/potassium phosphate buffer (100 mM, pH 4.0) gradient mobile phase. Previous met hods used for separating ipratropium bromide from its related compound s involved reversed-phase ion-pairing HPLC with UV detection. These me thods exhibited less reproducibility, less ruggedness and required a h igh flow rate. The reported method is linear from 10 to 1000 mu g ml(- 1) with a limit of detection of 60 ng ml(-1). In addition, analysis of samples subjected to accelerated stability conditions showed that all degradants are resolved from the active component, resulting in a sta bility-indicating assay. This assay also saved mobile phase and elimin ated problems associated with ion-pairing reagents. (C) 1998 Elsevier Science B.V. All rights reserved.