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.
Simms
P J
PJ
Product Development, Dey Laboratories, Napa, Ca 94558, USA.
Towne
R W
RW
Gross
C S
CS
Miller
R E
RE
D001993:Bronchodilator Agents / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006863:Hydrogen-Ion Concentration; D009241:Ipratropium / Q000302:isolation & purification*; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
D001993:Bronchodilator Agents; D009241:Ipratropium