NDSRI of Doxepin

Limits of Nitrosamines
1

FDA has described two NDSRI for Doxepin.

  1. N-nitroso-desmethyl-cidoxepin &
  2. N-nitroso-desmethyl-doxepin, (e)-
    Which NDSRI is to be monitored for Doxepin related drug Products ???
2

Both. E-Doxepin is an impurity of Doxepin leading to an additional NDSRI.

I would presume that if you can keep the primary NDSRI in check that the NDSRI based on the impurity will never be over 10% of the specification. If that is shown in the confirmatory testing, you would not have to test that NDSRI on an ongoing basis.

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3

Hi, @jason.brown

Doxepin is a mixture of (E) and (Z) stereoisomers with an approximate ratio of 85:15, according to Wikipedia. I think both are APIs. I dare to say that Cidoxepin or Z-Doxepin is a minor component. I am sorry for pointing out the details.

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4

Good catch, @Yosukemino & Wikipedia. The thought may still be true. Given the lower ratio, E may remain below 10% and not have to be tested. This is just not as likely as I supposed.

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