Stability Indicating HPLC Method Development and Validation

High performance liquid chromatography (HPLC) is an integral 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. Forced degradation studies of new chemical entities and drug products are essential to help develop and demonstrate the specificity of such stabilityindicating methods. In addition to demonstrating specificity, forced degradation studies can be used to determine the degradation pathways and degradation products that could form during storage, and facilitate during formulation, development, manufacturing and packaging. For marketing applications, current FDA and ICH guidance recommends inclusion of the results, including chromatograms of stressed samples, demonstration of the stability-indicating nature of the analytical procedures, and the degradation pathways of the API in solid state, solution, and drug product. A review of literature reveals that a large number of methods reported over the period of last 3 – 4 decades under the nomenclature ‘stability-indicating’, but most of the reported methods fall short in meeting the current regulatory requirements. Hence a systematic approach for the development of validated SIAMs that should meet the current ICH and regulatory requirements. . The following will provide some suggestions for performing forced degradation studies based upon available guidance from the ICH and FDA.