STABILITY INDICATING HPLC METHOD DEVELOPMENT – A REVIEW

Abstract

High performance liquid chromatography (HPLC) is an essential analytical tool in assessing drug product stability. HPLC methods should be able to separate, detect, and quantify the various drug-related degradants that can form on storage or manufacturing, plus detect and quantify any drug-related impurities that may be introduced during synthesis. This article discusses the strategies and the issues pertinent to designing stability-indicating HPLC methods for drug substances. It furthers understanding of the chemistry of the drug substance and drug product and facilitates the development of stability indicating analytical methodology. A number of key chromatographic factors were evaluated in order to optimize the detection of all potentially relevant degradants. An appropriate sample solvent and mobile phase must be found that affords suitable stability and compatibility with the component of interest as well as the potential impurities and degradants. The method should be carefully examined for its ability to distinguish primary degradants from secondary degradants. Forced degradation studies of new chemical entities and drug products are essential to help develop and demonstrate the specificity of such stability-indicating methods. Practical recommendations are provided for developing forced degradation protocols at every stage of drug development and avoiding common pitfalls that may confuse data interpretation.