ATNC analysis: securing products against the nitrosamine risk

The nitrosamine risk is a critical issue for pharma, biopharma, and cosmetics manufacturers. It can arise at different stages of the product lifecycle: raw materials, active substance, excipients, water, container-content interactions, manufacturing processes, cleaning, storage, or packaging. In this context, rapid identification of the analytical hazard is essential to document the risk assessment, confirm a suspected contamination, and prioritize corrective actions. ATNC analysis provides a global view of the total nitrosamine burden, complementing targeted analysis of specific compounds.

After the nitrosamine risk assessment, several levels of investigation can be deployed. Qualitative or semi-quantitative screening makes it possible to quickly detect a potential presence. Targeted quantitative testing can then precisely measure compounds such as NDMA, NDEA, NMBA, NEIPA, NDIPA, NPIP, NPYR, NMOR, NDELA, or other relevant nitrosamines depending on your product. This approach is particularly useful for finished products, raw materials, synthesis intermediates, and certain complex matrices.

Detecting nitrosamines at trace levels relies on high-performance chromatographic and spectrometric systems. Depending on the case, an expert laboratory may use equipment such as UPLC-MS/MS, Orbitrap-type LC-HRMS, LC-QTOF, GC-MS, and GC-MS/MS. These tools make it possible to carry out targeted analysis, presence/absence screening, investigations into unlisted nitrosamines, and studies on NDSRI impurities, with a high level of selectivity.

Working with an expert laboratory helps reduce analytical uncertainty and speed up decision-making. Support may include targeted nitrosamine analysis, the search for unlisted compounds, ATNC analysis, confirmation of results in a dispute context, as well as validation of very low quantification limits. This approach is particularly useful when matrices are complex or when quality and regulatory stakes are high.

An expert laboratory supports manufacturers from the initial assessment through to the production of data that can be used by quality, R&D, and regulatory affairs teams. Services may cover qualitative and semi-quantitative screening, targeted quantification of known nitrosamines, the search for specific nitrosamines not listed, the study of NDSRIs, as well as method development and validation according to ICH Q2 (R2). This approach makes it possible to address a wide range of needs: dispute investigation, compliance verification, validation of the quantification limit at very low levels, or securing a formulation or process change.

The choice of method depends on the nature of the sample, matrix interferences, the trace level being sought, and regulatory expectations. An expert laboratory can therefore propose a combination of techniques to ensure reliable results and achieve very low quantification limits, in the ppb range depending on the compounds and matrices. To explore sector-specific challenges further, also see the techniques to adopt for nitrosamines in pharma and container-content interactions in pharma and cosmetics.

Beyond the equipment, result reliability depends on method development, sample preparation, blank management, control of matrix effects, and analytical validation. Methods can be developed and validated according to ICH Q2 (R2), with verification of parameters such as specificity, linearity, accuracy, precision, robustness, and quantification limit. This rigor is essential for quality files, deviation investigations, and regulatory support needs.

For cosmetics manufacturers, analytical expertise can also be integrated into broader issues involving formulation, powders, nano-objects, or material-product interactions. Depending on your needs, you can also consult cosmetic powder analysis and cosmetic analysis according to ISO/TR 18811 and related approaches.

The ATNC analysis is relevant when a targeted search alone is not enough to characterize the hazard. This is especially the case when there are multiple formation pathways, formulation changes, processes likely to generate several nitrosamines, matrices for which not all species are known in advance, or when investigating diffuse contamination. By providing an overall estimate of total nitrosamines, it helps prioritize actions: confirm the need for additional analysis, compare several batches, assess the effect of a corrective action, or document a control strategy.