How do nitrosamines form?

Nitrosamines form when a secondary amine reacts with a nitrosating agent. The nitrosating agent is usually nitrous acid, which itself forms from nitrite under acidic conditions. The reaction produces an N-nitroso compound, which is the defining chemical feature of all nitrosamines.

That is the basic chemistry. What makes nitrosamines a widespread concern is how many different situations create the right conditions for this reaction to happen.

In pharmaceuticals

Nitrosamines can form during drug manufacturing when nitrogen-containing reagents, solvents, or intermediates react with trace nitrite impurities. They can also form in the finished product over time if the formulation contains both an amine-containing API and a nitrite source such as a contaminated excipient. This is why ICH M7 guidance now requires manufacturers to assess nitrosamine risk across the full manufacturing process, not just the final product.

Screening excipients for nitrite and nitrate content is one way to catch the problem early, before the precursors have a chance to react.

In food and drink

Nitrosamines can form during high-temperature processing of nitrogen-rich materials. In malting, kiln drying barley at high temperatures in the presence of nitrogen oxides produces NDMA. In cured meats, nitrite-based preservatives can react with amines in the protein matrix. In beer, trace NDMA from contaminated malt can persist through the brewing process into the finished product.

In cosmetics

Many cosmetic formulations contain amine-based ingredients such as diethanolamine (DEA) and triethanolamine (TEA), used as emulsifiers and pH adjusters. These can react with nitrosating agents present as contaminants or formed from other ingredients. The result is nitrosamine formation within the product, sometimes increasing over time during storage. NDELA is one of the most commonly detected nitrosamines in cosmetics.

In rubber and elastomers

Rubber curing (vulcanisation) uses accelerators that contain secondary amines. During the curing process, these amines can react with nitrogen oxides present in the environment or released from other additives, forming nitrosamines in the finished material. These compounds may remain in the product or be released as emissions.

In industrial processes

Amine-based systems used in carbon capture, gas scrubbing, and solvent recovery can generate nitrosamines as degradation products when the amine reacts with nitrogen oxides in the process stream. This is an emerging area of monitoring interest.

Why formation matters for testing

The reason nitrosamine formation chemistry matters is that it tells you where to look. If you understand the conditions that produce nitrosamines, you can screen for precursors, monitor at-risk process steps, and test finished products with the right level of sensitivity. Reactive ingredients, high temperatures, and the presence of nitrite or nitrogen oxides are the common warning signs.

Want to discuss nitrosamine risk in your process or product? Get in touch with the team.