USP Science & Research reposted this
#nitrosamines ... Are you dealing with N-nitroso-Ticagrelor in your product?? 🛑 Not TOO FAST!! 🛑 If you decide to skip risk assessment or your assessment is solely based on the letter/checklist provided by your supplier, or you relied on a Google search to ID your risk. 🌪️ You are about to embark on a wild ride!! This is one of the many nitrosamine examples that highlight why 1️⃣ a comprehensive risk assessment is necessary and 2️⃣ why collecting checklists and letters of 'free of nitrosamines' without the necessary supporting data is simply a waste of time, money, and energy! 🗑 More surprising is that commercial suppliers of reference standards offer this impurity as a product on their catalogs and websites, 'available for shipping'. What are they putting inside those vials if the molecule can NOT be synthesized? 😩 Learn about this case and sharpen your risk assessment skills at US Pharmacopeia Nitrosamines Exchange Community, a knowledge-based community for all things Nitrosamines. #nitrosaminas #nitrosamine #nitrosaminne #nitrosammine
Have you had experiences similar to this with other 'listed impurities'?
We Chemicea have more than 500+ nitrosamine impurities in stock. For the compounds like Ticagrelor and other electron deficient nitrogen cases where nitrosamine synthesis is not feasible we provide a comprehensive synthesis justification report. www.chemicea.com
Same is true of N Nitrosofelodipine.
The same is true for N-Nitroso Pazopanib. Although there are many suppliers on the Internet, if you order, they won't be able to synthesize the impurity and cancel your order after 6 months if you are lucky or let's say if they are honest. I think this is very bad for the pharmaceutical industry since the authorities started to question all these "impossible to synthesize nitrosamines" probably because of the web pages of these impurity suppliers where these nitrosamines were advertised as "available".
When Ticagrelor reacts with different Nitrosating agents, the resulting product is in fact 4,5-Dihydroisoxazole derivative that matches with the mass number of N-Nitroso-Ticagrelor. Spectroscopic techniques proton NMR, Mass not enough, 13C and 2D COSY etc required to confirm the structure. So don’t depend on COA and partial characterization data, ask for full data and review it.
Yes absolutely ...it's not possible to form this nitrosamine in the flask...
This situation is very interesting, although it is incredible, it is real. Another thing that would be very interesting to know is: How does this class of molecules end up on this list? Appendix 1 of the Q&A for marketing authorization of applicants... Naiffer Romero Raphael Nudelman Andrew Teasdale
Thanks for sharing
Very informative
Principal Scientist @ US Pharmacopeia | Nitrosamine Impurities & PGI SME
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