Avoiding unexpected nitrosamine contamination in pharmaceuticals

May 07 2025

In recent years, nitrosamine contamination has emerged as one of the most pressing challenges for pharmaceutical manufacturers. Following the detection of NDMA in valsartan in 2018, similar issues surfaced in ranitidine, metformin, and other products—leading to large-scale recalls, regulatory scrutiny, and financial penalties.

As regulators like the EMA and FDA now require comprehensive nitrosamine risk assessments, manufacturers face a difficult task: many nitrosamines can form from unexpected sources such as excipients, raw materials, packaging, or even during synthesis. Traditional targeted testing may miss these hidden threats.

Why conventional testing isn't enough

Most laboratories rely on targeted methods to detect known nitrosamines. But if a nitrosamine isn't on the list—or if it's formed through new pathways during production—it can easily go unnoticed. This leaves manufacturers vulnerable to undetected contamination and subsequent non-compliance.

A smarter approach: Apparent total nitrosamine content (ATNC)

Ellutia’s Automated Total Nitrosamine Analyser (ATNA) offers a powerful screening solution through ATNC analysis. Unlike targeted methods, ATNC testing detects all nitrosamines by identifying the shared nitrosamine functional group, without needing reference standards for each compound.

Rapid screening to ppb levels
Non-targeted detection catches unknown nitrosamines
Optimised chemistry eliminates false positives from nitrites
Unattended operation for up to 20 hours with high throughput

This makes the ATNA ideal for high-volume quality control labs that want to identify issues early, conserve analytical resources, and meet evolving regulatory requirements with confidence.

What happens if ATNC is high?

If the ATNA flags a high ATNC value, a follow-up analysis with GC-TEA or other methods can be used to identify the specific nitrosamines present. Ellutia’s GC-TEA system, with its ability to detect all volatile nitrosamines (including unknowns), provides the highest confidence in final confirmation.