Speaker
Description
ABSTRACT
Background
Due to public health and environmental concerns, controlling genotoxic impurities in pharmaceutical products is a regulatory requirement. Mass spectrometry (MS) is an analytical technique that can identify and quantify these impurities even in very small quantities due to their sensitivity, resolution, and accuracy.
Objectives
This systematic review therefore seeks to examine the mass spectrometric methods used to detect genotoxic impurities in pharmaceutical products to provide an array of validated MS procedures that can strengthen the monitoring and control of these potentially carcinogenic substances in pharmaceuticals.
Methodology
We searched online database published between 2008 and 2025. The results were reported according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines.
Key Findings
Ninety-seven (97%) reported using liquid-liquid extraction, 64% used liquid chromatography, while 35% used gas chromatography. Most papers used electrospray ionization (50%) and electron impact ionization (33%) techniques. Specifically, 37% and 58% used quadrupole or triple quadrupole mass analyzers, respectively, accounting for 95% of the studies reported in this review.In this review article, the genotoxic impurities identified include class 1, 2 and 3 without any impurities from class 4 and 5. Nitrosamines were the predominant class 1 reported by 33 out of the 44 articles. The levels of nitrosamines reported were in the range of 0.00869 - 68.8 ppm for N-Nitrosodimethylamine and 0.00623 - 0.157 ppm for N-Nitrosodiethylamine, which were outside the acceptable limit of not more than 0.12 ppm and 0.082 ppm, respectively. The levels of class 2 genotoxic impurities ranged between 0.5 – 37.5 ppm. The levels of class 3 impurities were not reported in these articles.
Implications
The exposure to high levels of nitrosamines in medicines (e.g., losartan and metformin) used for managing chronic diseases poses a serious public health risk, and there is therefore a need for stringent monitoring and regulation.