The determination of nitrosamines in all APIs and drug products is the new hot topic engulfing the pharmaceutical industry.

In 2018, Nitrosamine impurities including N-nitrosodimethylamine (NDMA) were first detected in blood pressure medicines ‘sartans’ leading to product recalls and a regulatory review. Since then, we have seen more cases of nitrosamines contamination for example in Ranitidine and Metformin, with further product recalls and reviews being carried out by regulatory authorities across the world.

Highly toxic, this class of compounds may unexpectedly be generated in many unrelated products

Nitrosamine Risk Assessment and Regulatory Guidance

The European Medicines Agency (EMA), US Food and Drug Administration and their regulatory counterparts around the world have set out detailed guidance recommending steps that manufacturers of APIs and drug products should take to detect and prevent unacceptable levels of nitrosamine impurities in products.

An internationally recognised acceptable daily intake limit for common needs nitrosamines has also been set. All commercially available pharmaceutical products should be risk assessed, with the submission of any necessary analytical work required to ensure that a drug substance and drug product is safe of nitrosamines.

The EMA has highlighted six key common nitrosamines to consider, though more unusual nitrosamines may be emphasised in the risk assessment. Those common nitrosamines include:

  • N-nitrosodimethylamine (NDMA)
  • N-nitrosodiethylamine (NDEA)
  • N-nitrosodiisopropylamine (NDIPA)
  • N-nitrosoethylisopropylamine (NEIPA)
  • N-Nitrosodibutylamine (NDBA)
  • N-Nitroso-N-methyl-4-aminobutyric acid (NMBA)

RSSL Nitrosamines Analysis Service

RSSL approach nitrosamine testing by using ultra-sensitive analytical instruments, combined with the most suited sample preparation technology, to extract the desired nitrosamine or nitrosamines from the product. The two main analytical techniques are:


Our LC-MS Triple Quadrupole (TQ) instruments are state of art, meeting the required sensitivity and specificity, even in complex pharmaceutical products. If required, a High-Resolution Mass Spectrometer (HRMS) will also be used to investigate the product further, enabling us to screen a product for those unusual and unique nitrosamines.

  • Gas Chromatography-Mass Spectrometry (GC-MS)

RSSL has a wide range pf Gas Chromatography–Mass Spectrometry (GC-MS) instruments, from headspace GC-MS, direct injection GC-MS and GC-QTOF instruments. This ensures that we can cover all the nitrosamines not observed by LC-MS, determining nitrosamines in high complex matrices, while also acting as a complementary and orthogonal technique.

RSSL’s pharmaceutical contamination and impurities team have extensive experience in nitrosamines, working closely with the industry and our clients to develop and validate bespoke analytical methods. We pride ourselves on our personal service and will be available for all project communications throughout the development and validation process ensuring your timelines are met. Whether you require a limit test, or a quantitative method from tablets, to aqueous formulations, to suspensions, we have the expertise to achieve your aim.

RSSL’s nitrosamine testing service is part of our comprehensive range of critical assessment services for pharmaceutical products which also includes Extractables and Leachables Studies and Impurity Investigations.

To watch the RSSL webinar "Nitrosamines Analysis - Better Understanding the Risk" on-demand please click here.

To find out more about our nitrosamines testing service or to discuss your testing requirements with one of our specialists please contact us.

Interested in this service?

News & Events

Make an Enquiry