N-nitroso-atorvastatin

N-nitrosamines Chemistry
1

Dear Community,

N-nitroso-atorvastatin is commercially available as an analytical reference standard; however, we could not identify literature describing its formation in atorvastatin drug substance or drug products, and it is not specifically listed in the EMA or FDA nitrosamine guidance. Is there evidence that this NDSRI can actually form in atorvastatin-containing products, and if so, what would be the expected formation pathway?

Thank you in advance!

2

Hi,

Is it really available? or is it listed in commercial webpages? I am not really sure if N-nitrosoatorvastatin would be easily synthesized, or stable.

I would recommend double checking characterization data (not just HPLC/MS) before actually buying

2 Likes
3

Yep, completely agree. Before purchase, I also would want to see the characterization data. The lack of availability vs “inquire” and lack of a CAS number throw up flags in addition to the structure itself. I likely would just rule it out entirely. See the discussion below on this topic.

N-Nitrosoatorvastatin and applicable potency category 4 or 5 - Limits of Nitrosamines - Nitrosamines Exchange

1 Like
4

Thank you both for the quick replies!

It is available for purchase on multiple websites, or at least it is possible to request a quotation. I don’t have much experience in this area, and I was asking because I am currently performing a nitrosamine risk assessment (for FP). We have nitrite present from the excipients, so I was wondering whether this could pose a risk for the formation of N-nitroso-atorvastatin.

I have now checked the structure of the compounds offered on these websites, and they are actually offering the corresponding N-nitrosAMIDE. However, this does not make me much less concerned, as my understanding is that some N-nitrosamides can also be carcinogenic.

5

You are right, nitrosamides can also be of concern (although outside of the current scope). Nonetheless, they are normally difficult to form, and in many cases, not very stable.

A Nitrosation test (NAP) can help you identify whether the formation is feasible or not. Available for purchase on websites is not a proof of it being possibly synthesized. Many vendors have grabbed all APIs with amines / amides and just added the NO. If there is interest, they will try. What I mean is that they may have never even attempted anything before putting them on the web

2 Likes
N-Nitrosoatorvastatin and applicable potency category 4 or 5