Separation Science, in collaboration with Agilent, offers a technology guide that provides key information for individuals looking to improve knowledge and analytical skills in the trace analysis of nitrosamines in pharmaceutical products. From expert insights to recent applications to tip and tricks, this resource is a great place to start your mutagenic impurities analysis journey.
Genotoxic impurities, and more specifically, mutagenic impurities in active pharmaceutical ingredients (APIs) and drug products pose a significant risk to patient health, even in trace amounts. These impurities can interact with DNA, leading to mutations and potentially cancer. APIs with structural moieties such as N-nitrosamine, hydrazine, epoxide, and aziridine possess a higher possibility of mutagenic activity.
Recently, regulatory agencies such as the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) detected N-nitrosamines impurities (NDMA, NDEA, NMBA, etc.) in several blood pressure medicines (sartans), as well as in heartburn and stomach ulcers medicines (ranitidine). These findings not only led to drug product recalls, regulatory actions, and loss of business, but also to the establishment of new, more stringent guidelines to evaluate mutagenic impurities. The proposed limits on these mutagenic impurity levels, both in drug substances and drug products, are well below the limits for non-mutagenic impurities as mentioned in ICH Q3A. To be compliant with these regulatory guidelines, sensitive analytical techniques are required to detect and quantify the impurity levels ranging from ppm to ppb.
Agilent offers both gas and liquid chromatography coupled with high sensitivity triple quadrupole mass spectrometry and high-resolution quadrupole time-of-flight mass spectrometry that can confidently help meet the global regulatory requirements for the detection and quantification of these N-nitrosamine impurities both in the API and final drug product.
