Analysis of Nitrosamine Impurities

An increasing number of raw and finished batches are found to be contaminated with nitrosamines. Nitrosamines are a class of carcinogenic impurities formed by the reaction of secondary amines, amides, carbamates, derivatives of urea and nitrite, or other nitrogenous compounds with nitrogen in the +3 state. Nitrosamines are classified as class 1 impurities in some fields, i.e., "known mutagenic carcinogens," based on rodent carcinogenicity and mutagenicity data. In drugs such as sartan, which contains a specific ring structure (tetrazolium ring), nitrosamine impurities may be produced during the synthesis process under certain conditions when certain solvents, reagents and raw materials are used. In addition, impurities may also appear in some products if contaminated equipment or reagents are used in the manufacturing process.

What are the Known Causes of Nitrosamine Impurities in Products?

• Use of sodium nitrite (NaNO₂) or other nitrifying agents.
• Use of contaminated raw materials (e.g., solvents, reagents, and catalysts) in the API manufacturing process.
• The use of recycled materials (such as solvents, reagents and catalysts).
• Use of raw materials and intermediates contaminated with nitrosamines.
• Cross-contamination due to different processes running on the same line.
• Degradation processes of starting materials, intermediates and drugs. This may also occur during the formulation or storage of finished products.
• Use of certain packaging materials.

Our Services

CD Formulation offers testing for nitrosamine impurities, for which the following testing requirements apply.

Manufacturers must be aware of the possible sources of nitrosamine formation during the manufacturing process and take appropriate control measures to reduce the potential for the formation of these carcinogenic impurities. The pharmaceutical industry needs to go beyond superficial phenomena and recognize that the quality of reagents and solvents, especially those used relatively upstream in the manufacturing process, are critical to ensuring the quality of the final drug.

Standards to be Met for Testing

Regulatory agencies are setting interim standards based on the maximum daily intake and will lower that limit in the future with the expectation that manufacturers will ensure complete freedom from nitrosamine impurities.

Why Choose CD Formulation?

The analysis of nitrosamines can be challenging. These ultra-low levels of impurities must be quantified in a variety of complex matrices.

Equipped with all the equipment needed to meet these limitations, including LC/MS and GC/MS systems.

Our laboratory specializes in the development and validation of highly sensitive and specific methods to assess carcinogenic impurities in pharmaceutical products. During pharmaceutical method development, we are often challenged with low detection levels, difficult matrices and unknown impurity identification.

In addition to experienced drug impurity analysis, we can also address the needs of extract and leachate detection, elemental impurity analysis, etc.

If you have a requirement about our services, please contact us by phone or email, our colleagues will reply to you within three working days.