Isolation and Identification of Process Related Impurities and Degradation Products from Pharmaceutical Drug Candidates, Part I

The objective of this two-part review article is to provide guidance for isolating and identifying process related impurities and degradation products from pharmaceutical drug candidates. The identification of degradation products can provide an understanding of impurity formation and define degradation mechanisms. If the identification process is performed at an early stage of drug development, there is adequate time for improvements in the drug substance process and drug product formulation to prevent these impurities and degradants long before the filing stage. Impurity and degradant structure elucidation is a collaborative effort involving the analytical chemist, process chemist and/or formulator as well as the degradation, mass spectrometry and NMR experts. The process described in this two-part article uses a designed approach for the impurity and/or degradant identification, which focuses on efficiency so that the success of data collection is maximized. There are a number of activities other than collecting experimental data, even though the experiments are central to the process. Part I of this article describes a process for isolating unknown impurities and degradants, while Part II will illustrate the role of mass spectrometry and NMR in the identification process.