Acta Pharm. 50 (2000) 185-193
The stability of several 1,4-benzodiazepines in solution was compared using a correlation analysis approach. Substituent sigma constants were used as quantitative descriptors of structure characteristics and were related to degradation kinetics of the drugs under study. Additionally, chromatographic retention factors of the drugs and their degradation products were applied in a similar way, correlating solvent effects with degradation rate constants. In an attempt to predict the relative stability of several 1,4-benzodiazepines in aqueous solution, it was found that relatively simple correlation models could be successfully applied using published substituent constants, as well as experimentally derived parameters.
Keywords: 1,4-benzodiazepines, solution stability, correlation analysis, liquid chromatography