Differential pulse polarographic determination of [R-(Z)]-α-(methoxyimino)-1-azabicyclo[2.2.2]-octane-3-acetonitrile monohydrochloride in tablets following derivatization with dimethyldioxirane

Abstract

Dimethyldioxirane was used as a derivatizing agent to convert [R-(Z)]-α-(methoxyimino)-1-azabicyclo[2.2.2]-octane-3-acetonitrile monohydrochloride (I) to the corresponding quinuclidine N-oxide which was then determined by differential pulse polarography in the presence of common excipients. The polarographic method yielded an LOD of 1.2 µg ml^–1 calculated from the linearity plot by conventional statistical means. However, by increasing the pulse amplitude to 100 mV, a 5.0 ng ml^–1 solution could be detected. This constituted an approximate eight-fold improvement over conventional HPLC procedures. The method was suitable for dosage forms containing I at levels as low as 100 ppm. Samples were extracted with phosphate buffer solution of pH 7.0, diluted into Britton Robinson buffer solution of pH 3.0 and the polarographic response recorded at a peak potential of –0.97 V. The method was linear over the sample concentration range of 0.05 to 25 µg ml^–1 with r= 0.9993. The precision for the determination of I at the 100 ppm level was 0.5%.