Nitrosamines are substances with an N=O (N-nitroso) functional group, and are considered to be highly toxic. Early analytical procedures had relied mainly on chemical reactions and spectrophotometric methods, which could indicate the presence of nitroso compounds but lacked the required specificity and sensitivity for targeted quantitation. Recent interest in nitrosamine testing increased sharply following the discovery of nitrosamine impurities in pharmaceutical products, including Sartan medicines, in 2018. This resulted in the rapid development of methods capable of detecting extremely small quantities (ppb) of these impurities. Liquid chromatography–mass spectrometry, particularly tandem mass spectrometry (LC–MS/MS), is now the accepted instrumentation used for both screening and confirmatory analysis.
The European Pharmacopoeia (Ph.Eur.) recently introduced General Chapter 2.5.42. N-Nitrosamines in active substances and medicinal products (01/2026:20542), which includes screening procedures for the specific nitrosamines; NDMA, NDEA, NDBA, NMBA, NdiPA, NeiPA and NDPA, with a compliance limit of 30 ppb. However, recent developments have shown a shift away from generic screening procedures toward a risk-based, validated approach targeting specific nitrosamines likely to be present in samples, as is evidenced by the PhEur publication of several substance-specific Certificates of Suitability (CEPs), including analytical methods for specified nitrosamines in specified sample types. The projects department at Butterworth has not only advanced equipment but also proven practical experience to support our clients with nitrosamine development and routine work, including full validation for regulatory submission.
Why Choose Butterworth Laboratories?
- Butterworth has state-of-the-art LC-MS/MS instrumentation required for nitrosamine analysis.
- Butterworth has previous experience in developing and validating procedures for nitrosamine analysis suitable for regulatory submission.
Frequently Asked Questions
Yes
Yes
In many cases, this should be possible.
Again, in many cases, this should be possible.
Yes, where validated methods are available.
This would depend on the results of a risk-based assessment.
