Stability Indicating Analytical Methods

Stability indicating analytical method is a crucial part of a development program and, eventually, the chemistry, manufacturing, and controls (CMC) part of an IND filing. The development of a suitable stability indicating method provides a rigorous foundation for the pre-formulation studies, drug substance and drug product stability studies, and the development of proper storage specifications. It is typical that one stability indicating method is designed as a “process method”, and is used to assay manufactured drug substance for purity and presence of impurities. A complimentary and frequently unrelated method, is developed to monitor degradation of a drug substance, for example its compatibility with components of a formulation.

In development of a stability indicating analytical method a separation technique is adapted to resolve the analyte of interest from impurities, degradation products, and excipients.  The most common technique used for this purpose is liquid chromatography.

A stability indicating method is necessary for a successful drug development program.  Frequently, two such methods are developed.  A “process” method is used for determination of purity of synthetic drug substance and synthetic intermediates, and may be available from the manufacturer.  A “degradant identification” stability indicating method should be orthogonal to the “process” method and is designed to separate the peak of the analyte from those of degradation products or related substances.  Ideally, peaks due to individual degradants also should be resolved for identification purposes.

WLI develops and qualifies stability indicating methods based on HPLC and HPLC-MS analytical techniques.  Since pure samples of degradation products are rarely available, forced degradation studies are undertaken that mimic the degradation/decomposition of the drug substance under a wide range of conditions.

WLI can develop new methods or modify existing methods to be stability indicating.  WLI supports technology transfer activities on behalf of the client, when installation and operation of methods at GLP/GMP facilities is required.

WLI develops stability indicating methods with a variety of drug substances, including small molecules, peptides, proteins, oligonucleotides, and cytotoxic materials.