A critical appraisal of drug stability testing methods.

The determination of potency or shelf life, impurity limit testing, and study of reaction mechanisms are considered as different aspects of drug stability. These aspects traditionally have been treated in isolation. The current criterion for a stability-indicating assay is criticized and the merits of choosing reactant or decomposition product for monitoring decomposition are discussed. The initial-rate method of determining reaction order and rate constants by analysis of decomposition product is described and its potential advantages over traditional integral methods are discussed. Examples of the application of the initial-rate method to simple and complex drug decomposition systems for the determination of decomposition rate constants are given. Applications to limit testing and study of reaction mechanisms are outlined and the dependence of the initial-rate method and decomposition product analysis on modern chromatographic methods is emphasized.