Spotlight on: Nitrosamines

What are nitrosamines?

Nitrosamines are a large group of N-nitroso compounds that share a common functional N-N=O group. They are produced by a chemical reaction between a nitrosating agent and a secondary or tertiary amine. Back in 2018, nitrosamines suddenly found themselves in the spotlight when they were unexpectedly detected in medications for high blood pressure. Since then, they have been found in several other prescription medications, including those for heartburn, acid reflux and diabetes, resulting in manufacturers recalling some common medications.

How are nitrosamines and related impurities detected?

US FDA-approved methods use both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), depending on the volatility of the analyte.

The sub-group of nitrosamines known as NDSRIs are more challenging to analyze as they are often present at lower concentration levels, which require very sensitive mass spectrometry instruments to meet the regulatory guidelines for acceptable intake limits.

Why are nitrosamines a concern?

Some nitrosamines may be carcinogenic to humans, increasing the risk of cancer if exposure is above acceptable levels and over prolonged periods of time.

It is also now known that if the active pharmaceutical ingredient (API) has a secondary amine, a nitrosamine can form that is unique to this individual API. These compounds are known as nitrosamine drug substance-related impurities (NDSRIs).*

_{*https://www.fda.gov/consumers/consumer-updates/what-know-and-do-about-possible-nitrosamines-your-medication}

Using LC-MS-based test procedures

The analytical process is a key step in maintaining drug safety, where regulatory compliance is also required. This is a time-consuming process to track and audit along with maintaining the qualification status of the system. With our renowned sensitivity, robustness and accuracy, SCIEX LC-MS systems are uniquely qualified for analyzing the complex nature of nitrosamine and related impurities and achieving the quantitative limits required. In addition, our compliance-ready SCIEX OS software offers the flexibility to tailor and deploy security policies that meet regulatory requirements.

Why are nitrosamines and related impurities so challenging?

Nitrosamine impurities can form at many stages, with sources ranging from manufacturing and storage proccesses to raw materials such as solvents, reagents and intermediates
Performing risk assessments for the potential presence of nitrosamine impurities is challenging due to this variety of possible sources
Analytical methods to test for these compounds must be validated
NDSRIs are similar to their APIs and are typically present at very low concentration levels

SCIEX is there where it counts

Successful nitrosamine impurity analysis that meets regulatory requirements depends on robust and sensitive quantitative performance combined with compliant processes. With SCIEX solutions, you can:

Achieve robust and sensitive identification and detection of nitrosamines and related impurities
Benefit from precision quantitation with reliable and resilient instrument performance
Simplify nitrosamine impurity analyses with intuitive, compliant-ready software

How SCIEX is progressing the quantitation of nitrosamine impurities in a metformin API

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Understanding the analysis of genotoxic nitrosamines in losartan

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Unveiling the analytical insights into nitrosamine drug substance-related impurities (NDSRIs)

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For a deeper dive into nitrosamines and technical content that spans a diverse range of molecules and challenging compounds, please explore our new quantitation content library

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