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Methods to Inhibit Bacterial Pyomelanin Production and Determine the Corresponding Increase in Sensitivity to Oxidative Stress
Published on: August 31, 2015
A prediction system of oxidation reaction as a solid-state stress condition: applied to a pyrrole-containing
Yoko Kawaguchi-Murakami1, Naoto Fukutsu, Toshi Kajiro
1Analytical and Quality Evaluation Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan. si.schroeder@tu-bs.de
Abstract:
Stress conditions for predicting oxidative degradation products in solid-state pharmaceutical compounds were investigated. 4-Methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl)pyrrole, Compound A, was used as the model compound for this study and its four main degradation products were due to oxidation, as identified by LC-MS and LC-(1)H NMR. In order to develop a prediction system for the oxidation reaction, solid-state Compound A was stored under moisture-saturated conditions. Hydrogen peroxide was added to the solution used to saturate the headspace with moisture and oxygen was substituted for the headspace air, in order to stimulate the oxidation reaction. After optimizing the conditions, a similar degradation product profile to that actually observed in the stability studies was obtained in only 3 days under conditions using 3% hydrogen peroxide at 40 degrees C. The prediction of the oxidative degradation products in a solid-state pharmaceutical compound was successfully achieved in a short term utilizing this newly developed prediction system.
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