Stability-Indicating Spectrophotometry Determination of Morphine in Injectable Solutions Containing Bisulfite

Abstract

Morphine in injectable preparations mar undergo reaction with bisulfite when this is used as an antioxidant in the formulation. A simple chromatographic procedure has been developed for the separation of morphine from its oxidation products and from the morphine-bisulfite interaction products. Neutral or acidic impurities are removed from a pH 4.3 buffered sample by elution of a partition chromatographic column with ether. An ether solution of di-(2- ethylhexyl) phosphoric acid is then used to elute the morphine as the cationic component of the ion pair. This fraction is extracted with dilute sulfuric acid to dissociate the ion pair and transfer the morphine to the acid solution for spectrophotometric determination. Multiple analyses of a commercial morphine sulfate formulation gave 101.2±0.3% of declared. Assays by 5 analysts of another commercial preparation and a laboratory preparation gave, respectively, an average of 99.6±2.7% of declared and an average recovery of 90.4±0.5%. The latter, containing 7 mg bisulfite/ml, or 7 times as much as the commercial formulations, shows significant bisulfite-induced decomposition.