Enantioseparation of tropa alkaloids by means of anionic cyclodextrin-modified capillary electrophoresis.

Anionic cyclodextrins (CDs), i.e., sulfated CD, sulfobutylether beta-CD (SBE-beta-CD) and heptakis(2,3-di-O-acetyl-6-sulfato)-beta-CD (HDAS-beta-CD), were used to separate the isomers of atropine, homatropine, ipratropium, scopolamine and butylscopolamine. Variations in the pH value and the concentration of the various CDs revealed the sulfated beta-CD to be superior to the other derivatives. In a basic medium at low concentrations of sulfated CD the enantiomers of atropine, homatropine and ipratropium were well resolved in a short migration time, which is appropriate for the routine analysis of the enantiomeric excess. Scopolamine and butylscopolamine compounds could not be separated with either CD.

The separation of ipratropium bromide and its related compounds.

Ipratropium bromide, the active component in ipratropium bromide metered dose inhalers (MDI), is used as a bronchodilator for the maintenance and treatment of bronchospasms associated with chronic obstructive pulmonary disease (COPD). The separation of ipratropium bromide, tropic acid, N-isopropyl-nor-atropine (NINA), 8-s ipratropium bromide, apo-ipratropium bromide and the excipients found in the formulation is important for analyzing raw materials and stability samples. We now report a reversed-phase HPLC method that can be used for separating ipratropium bromide and its related compounds, using an acetonitrile/potassium phosphate buffer (100 mM, pH 4.0) gradient mobile phase. Previous methods used for separating ipratropium bromide from its related compounds involved reversed-phase ion-pairing HPLC with UV detection. These methods exhibited less reproducibility, less ruggedness and required a high flow rate. The reported method is linear from 10 to 1000 micrograms 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 stability-indicating assay. This assay also saved mobile phase and eliminated problems associated with ion-pairing reagents.