A community member brought to my attention that there is a reference material supplier that is currently offering Synthesis Attempts and Failure Reportsā¦ I know organizations have used these types of reports to justify the derisking of particular nitrosamines. I imagine the depth of this report has to be significant for a regulatory body to accept, including all the characterization and analytical evidence.
I have not seen any of these āfor-purchaseā reports, so I cannot speak on their rigurosity. I wonder if anybody has had experience with these types of off-the-shelf reports.
Dear Naiffer,
is just some days ago that we have asked for this type of a failure report from an impurity supplier.
The draft sample which have been send to us was very nice with a lot of information regarding synthetic trials and identification data.
In this sample it was noticeable that they have also implemented the 3-armed nitrosation based on the paper of I. W. Ashworth et al (Approaches and Considerations for the Investigation and Synthesis of
NāNitrosamine Drug Substance-Related Impurities (NDSRIs). Org. Process Res. Dev. 2023, 27, 1784ā1791.
Here is a part of the content from the sample report (only two out of 10 synthetic trials is presented here)
I didnāt want to be seen advertising any particular company on LinkedIn - it shouldnāt have taken a lot for people to have been able to find who was offering this service for themselves.
I donāt know if this is from the company I had seen, but it looks a promising, positive start.
We are also working on a similar topic. For some nitrosamine impurities, we believe they are unlikely to form under practical conditions. Typically, we apply classic nitrosation reaction conditions and monitor the reaction using LC-MS to check whether the target molecular weight appears. Based on these results, we assess the likelihood of nitrosamine formation.
Our goal is to compile a public report listing APIs for which nitrosamines could not be generated, along with our experimental data. We hope this can help reduce redundant research efforts in the community. Weāve shared some of these reports with our clients, and the feedback so far has been quite positive.
However, weāre unsure whether such a report would be considered sufficiently comprehensive. If there is any suggestions on how we could improve it or make it more broadly useful?
