Preventing nitrosamines: Assessing risk today can eliminate testing tomorrow.
Nitrosamines are a hot topic, especially in the world of pharmaceuticals. But did you know that by monitoring their precursors through the various stages of manufacturing and in APIs, raw materials, excipients and water, you can significantly reduce the risk of formation of nitrosamines in a drug product?
Why is nitrosamine impurity analysis important?
Nitrosamines, or more correctly N-nitrosoamines, refer to any molecule containing the nitroso functional group. These molecules are of concern because nitrosamine impurities are probable human carcinogens.
The unexpected finding of nitrosamine impurities in drugs such as angiotensin II receptor blockers (ARBs), ranitidine, nizatidine, and metformin, has clarified the need for a risk assessment strategy for potential nitrosamines in any pharmaceutical product at risk for their presence. Stringent regulatory guidance’s are not only helping to make drugs safer, but through the method requirements are helping laboratories to identify the appropriate tools needed for accurate and confident analysis.
How are nitrosamines formed?
The presence of nitrite in the manufacturing process can represent a risk for NDMA formation if a secondary or tertiary amine is present. Read more about the formation in this Application Note (#73987). Therefore, it’s important to limit the nitrite and amine levels in drug substances and drug products.
What analytical tools are required?
Nitrosamine impurity analysis requires robust and sensitive analytical methods to ensure confidence in the obtained results. The wide Thermo Scientific portfolio is proven to be excellent for nitrosamine analysis, ensuring your exploratory and routine methods are performed as accurately and reliably as possible while maintaining requirements from regulatory bodies worldwide. Our major products for the analysis of nitrosamines include:
- Liquid, gas, and ion chromatography for robust separation
- High resolution, accurate mass (HRAM) mass spectrometry for ultimate confidence avoiding false positive results
- Tandem mass spectrometry, the best tool in routine analysis
- Single, compliance-ready software solution for all our technology solutions
Any new methods available?
A method was developed to determine nitrite in pharmaceuticals by coupling ion chromatography (IC) with UV absorbance detection. Read about it here. This method should be applicable to the determination of nitrite throughout the drug manufacturing process to assess the likelihood of nitrosamine formation.
Want more information on preventing nitrosamines?
Here are some more online resources:
Dionex ICS 6000 HPIC
Chromatography columns and cartridges
Chromeleon™ Chromatography Data System (CDS) software
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