Quantitation of Genetox Impurities Using a Surrogate Standard Approach

Abstract

With the ever increasing complexity of active pharmaceutical ingredient (API) preparations, more potential genotoxic impurities (PGI's) are being observed. It is thus necessary to determine if these PGI's are present in the final API's, and if they are present, to ensure the levels are acceptable for any clinical uses. For PGI's that have authentic standards available, quantitation can be accomplished in a straightforward manner. However, for PGI's that are expected to form through rearrangements or side reactions, authentic standards may not be readily available, significantly complicating the analysis. In this study we describe a surrogate standard approach for quantifying PGI's that allows for relative response factor calculations of PGI species utilizing both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS).

Applications of TiCl3 as a Diagnostic Reagent for the Detection of Nitro- and N-Oxide-Containing Compounds as Potentially Mutagenic Impurities Using Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry

“…The use of ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC/HRMS) is one of the most common analytical methods for the detection and characterization of PMIs. , Compounds containing nitro and N -oxide functionalities are often present as byproducts or impurities during the drug manufacturing process . These moieties are two of the key structural alerting functional groups of PMIs .…”