Low Level Impurities in Drug Substances and Drug Products and the Analytical Challenges in Identification and Quantitation

Abstract

Impurities that are seen in the active pharmaceutical ingredients (API) and the degradants that are seen in the drug products are to be identified and quantified according to regulatory requirements, especially when they are recurring ones and above the threshold limits that are described in guidance documents such as the ones from International Conference on harmonization (ICH). The identification and quantification of these impurities become even more important, especially when they could potentially have safety related adverse implications such as genotoxicity. Impurities such as the genotoxic ones and/or others that are potentially unsafe need to be controlled to very low levels or to be eliminated, typically in the order of parts per millions (ppm). This is usually a very challenging endeavor to come up with analytical techniques that have detection systems and methodologies that are very sensitive to support very low levels of detection (LOD) and quantitation (LOQ). This article discusses the implications of such low level impurities in the API and DP and the associated analytical challenges in identifying and detecting these impurities.