Prediction of Stability in Pharmaceutical Preparations XIII

The kinetics of solvolysis of the antibiotic porfiromycin are quantified in the pharmaceutically useful pH ranges in acetate, phosphate, and borate buffers. The devised ultraviolet spectrophotometric assays of solution degraded antibiotic are correlated with the plate-disk assay against S. aureus and the paper chromatographic assay against S. lutea . General acid catalyzed solvolysis is indicated as well as specific acidbase. In acetate buffers, the primary degradative mechanism is the hydrolysis of the fused ring aziridine group, whereas mild alkali substitutes a hydroxyl for the quinoid ring amine. In the intermediate pH ranges characterized by phosphate buffers reaction at both sites is implied and maximum stability at pH 8 at 30° can be predicted. Conditions for isolation of solvolytic products and their characterizations are given.