Impurity and Degradation Product Identification

Identification of impurities and degradations products is allowed by proper development of stability indicating methods. 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. Identification of impurities provides data for improvement of purification methods and for setting release specifications. Identification of degradation products provides important information on degradation pathways, excipient compatibility, storage conditions, and other considerations.

WLI operates a modern ion trap/triple quadrupole Applied BioSystems 4000 mass spectrometer, which is mated to an HPLC system.  We routinely use our HPLC-MS/MS capabilities to profile and identify unknown sample components. 

An impurity identification study may be an extension of a stability-indicating method development program,  a part of a program to identify leachable/extractable impurities, or a stand-alone project.  An example of an impurity identification project is confirmation of structure of a synthetic byproduct discovered in a new batch of API. 

Typically, our approach involves installation of a suitable HPLC method or modification of an existing method for use with volatile buffers that are compatible with a mass spectrometer.  The goal is to assure adequate separation of the active ingredient and the impurity or degradation product(s).  Once separation is achieved, we obtain the full scan and MS/MS spectra of the active ingredient, additional standard, and the impurity/degradation product(s) of interest.  This approach helps develop a relational understanding of molecular structure to mass spectrometric fragmentation patterns, which then are used to identify putative structures.

WLI provides impurity and degradation product identification work with a variety of drug substances, including small molecules, peptides, proteins, oligonucleotides, and cytotoxic materials.