N-nitroso Torasemide Impurity formation and control

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24

In our case, I confirm that it is very difficult discriminate a “fake” N-nitroso Torasemide standard (MW 377.46) from the hypotetical N-nitroso Torasemide (MW 377.42). We believe that the supplier made an honest mistake.
However the NMR confirmed that the structure does not correspond to the hypotetical N-nitroso Torasemide.
We will evaluate other suppliers, but we believe that no one obtained the correct substance.

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25

Did you use 1H-15N HSQC as 2D NMR?

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dear ccdw,
first of all, happy new year :smiley:
regarding the ‘‘fake’’ N-nitrosoticagrelor, we did not performed any NMR studies in our edge. All the information came from our API manufacturers. In their technical assessments, several NMR technics have been applied.
Among them, 1H-15N HSQC and 1H-15N HMBC experiments were performed.
have a nice day

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Thanks, I share the opinion that these are the go-to 2D NMR methods for these cases.
I had to use it a few times as well in such cases, but to my surprise initially not all NMR facilities had these type of measurements pretested to offer as services.

Best wishes.

28

Hallo to the team,
please let me bring back again the issue of N-nitrosotorasemide.
Is anyone in this group that had purchased a ‘‘real’’ reference standard of it finally? The last one we received was ‘‘faked’’ and had similar issues with the case of paliog
Now we received a question/request from a client for confirmatory tests based on the existence of relevant reference standard in the market!!
thank you
Christos

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Yes, during stability of the API there is chances of formation and leads to impact on during product as well.
Multiple times basis of theoretical data, impurity can be possible whereas practically synthesis of impurity doesn’t found success.

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Dear Shirish,
how do you know that it appears during stability?
Do you have a method analysis for this?
And if yes, do you have a ref. standard of N-nitrosotorasemide?
thanks
Christos

31

All our accountable suppliers have agreed that N-nitrosotorasemide is not obtainable as a standard. Their synthesis experiments did not yield a reliable molecule to be used as an analytical standard.

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32

Dear All,

On FDA Website, limit of N-nitrosamine Torsemide is given as 1500ng/day

I tried many ways to prepare the N-nitrosamine torsemide impurity but failed to get this impurity in lab. I did not detect the mass of N-nitrosamine torsemide during all the possible routes to get this impurity.

So, I am looking for the standard of this impurity.

It will be great help for me if you confirm weather this impurity actually exist or not ?

I am also looking for the vendor who synthesis this impurity and can support on this impurity .

I will be very thanks to you for answering my query .

Thanks ,
Amit Kumar Taneja

33

Thanks for sharing… can you please provide additional information on your providers attempts to synthesize the compound? I’m leading an internal project in USP and that information would be valuable.
Thanks

Naiffer

34

Dear Amit,
in the last two years we received two indipendent failure report from two different laboratories. Moreover, in Dec.2023 we purchased a reference standard which not really was the claimed “N-nitroso torasemide”.
We concluded that “N-nitroso torasemide” cannot be formed.
Kind regards

3 Likes
35

Dear Pailog,

Thanks for your prompt reply. Can you please share the company name from where you received the failure report . I will contact to that company for failure report .

Regards,
Amit

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One of them is Veeprho: Synthesis Attempts and Failure Report 🧐 - #19 by Yosukemino

1 Like
37

Dear Mircea Florea,

Thanks for support and valuable information

Regards,
Amit