In 2018, major recalls were triggered due to the presence of elevated levels of carcinogenic nitrosamines in multiple sartan-class drug formulations. Since then, there has been a renewed focus among regulatory agencies and pharmaceutical companies to reduce or eliminate the presence of these compounds in medicines.  This effort requires developing sensitive and reliable analytical methods to detect these compounds. Unfortunately, the LC-UV assays that are ubiquitous for pharmaceutical analysis provide inadequate sensitivity for detection at the trace levels (sub ng/mL) required to demonstrate adequate control of nitrosamine content. Conversely, mass spectrometers have shown detection capability down to the low pg/mL, level making it a suitable technique for the detection of these compounds. Recent literature has discussed the possibility of false positive detection of nitrosamines with mass spectrometry due to the presence of isobaric compounds that do not contain the N-nitroso functional group of concern. Again, mass spectrometry provides a solution to this undesirable problem because it provides an extra degree of specificity over UV-chromatographic-based methods by enabling multiple stages of mass-targeted fragmentation. As more investigation into the safety and relevance of novel nitrosamines (i.e., those derived from the active pharmaceutical ingredient) occurs, researchers have been documenting the unique mass spectral characteristics of these molecules. The work herein supports and further investigates the work published in 2021 by Asare et al. A discussion on overcoming false positive identification and implementing these characteristic fragmentation pathways to support quantitative method development will also be presented.

Characteristic fragmentation patterns of novel nitrosamines via HR-MS/MS

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.