PRACTICAL OPTIMIZATION OF AN ION-PAIR HPLC ASSAY FOR O-6,7,8,9,10,12-HEXAHYDROAZEPINO[2,1-B]QUINAZOLINE MONOHYDROCHLORIDE BULK PHARMACEUTICAL CHEMICAL

An ion-pair HPLC method was optimized for the assay of the experimenta l Alzheimer's bulk pharmaceutical chemical CI-1002 Hydrochloride and t en potential impurities. The process of selecting the most robust chro matographic system (i.e., mobile phase composition, pH and column) was completed. A mobile phase consisting of aqueous sodium dodecyl sulpha te (SDS) and methanol was utilized. Several commercially available bas e-deactivated C-18 columns were evaluated and a Waters Symmetry 150 x 4.6 mm, 5 mu m particle size column was selected. The Waters Symmetry column was used in subsequent experiments to optimize the mobile phase pH, the percent methanol, and the SDS content. The ruggedness of the HPLC method was evaluated by documenting slight modifications under co ntrolled conditions. The ion-pairing method enables the assay and impu rity profile for ten potential impurities to be carried out simultaneo usly. The method also provides baseline resolution for all components and a run time of approximately 30 minutes.