N-nitroso-rivaroxaban amide

Confirmatory Testing & Analytical Challenges
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Hello everyone ,
We have the challenge to separate the N-nitroso-rivaroxaban amide from API rivaroxaban with HPLC, which is the new NDSRI in appendix of EMA&FDA. Anyone have the experience regarding this impurity ? much thanks !!!

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Dear Pu Zhao

We also working on separation of N-Nitroso Rivaroxaban amide impurity from Rivaroxaban Active peak. However it was very challenging to separate and still we working on with different column chemistry and diluents selections, So far not successful.
Dear Nitrosamine experts

We are looking forward your suggestions, how can convince agency regarding this impurity exemption?
if API ROS is not supporting to form this impurity.

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Even if the ROS does not support, you can check for the presence of the precursor amine in the stress degradation data…

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Hi, it is very interesting to find the separation challenge. What’s the problem here? Is there a very similar polarity peak interfering or the whole reaction is very massy? I’d like to offer help, if possible.

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Hi ，
We have made some small progress in our research, separation method using normal phase chromatography, chiral columns and VWD detector .
The biggest problem is the sample solution is not completely dissolved and the sensitivity of the method (NP not suitable for LC-MS).

Chromatogram for information:

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Hi,
Kindly use phenyl column. With 0.1% formic acid and methanol as mobile phase. We got better seperation of both impurities and Rivaroxaban peak. Got desired recovery on drug product.

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Hello everyone ,
We have the similar challenge to separate the N-nitroso-rivaroxaban amide impurity from Rivaroxaban API using LC-MS, which is the new NDSRI in appendix of EMA&FDA. We have attempted several chromatographic columns, mobile phase compositions, literature articles, proposed conditions as available in this forum, but none of them could give us the positive outcome. It would be great if anyone can help us by sharing their experiences / suitable method conditions to separate Nitroso Rivaroxaban Amide Impurity from Rivaroxaban.
Thank you in advance.