Estimation of Nitrosamines from Nitrites level

[desaimayur78]

Hello,
Can any one guide how to calculate Nitrosamines from known level of Nitrites.

[Naiffer_Host]

@desaimayur78 you can check a great example of how the nitrate content in excipients is use to predict theoretically nitrosamine in @schlinjo1975 paper:

How to avoid NDMA in Metformin? (In press)

Back in October 2020, we saw an increased concern about the potential presence of NDMA in Metformin. @trust_user_a @trust_user_b @trust_user_c “As of October 2020, EMA and the national competent authorities are asking marketing authorization holders for metformin-containing medicines to test their medicines before releasing them onto the market,” said EMA’s Committee on Human Medicinal Products (CHMP) in an update to its post-authorization nitrosamine impurity testing procedures” As a Nitros…

@Yosukemino can you refer us to the post you did on the case of GSK?

[Yosukemino]

Sure, @Naiffer_Host. It reflected the strategy of EFPIA workflow ver1.0.

Lactose, Nitrosamine Risk?

I share the good example of nitrite calculation contained in excipients and others demonstrated by Dr. Urquhart in nitrosamine workshop last week. [nitrite in excipient] According to him, contamination risk is evaluated with 100% conversion at first. Next a conversion factor, whose detail is not included here, is considered and the calculated value is compared with (adjusted) ADI. This example may concern with API with secondary or tertiary amine, however if the amount of these amines is at …

And I add the link to the relevant section on Vimeo. I hope it will help you, @desaimayur78.

[jason.brown]

That looks like a great video overall as well. Thanks for sharing.

[krystynakk]

Dear Yosukemino,
I am new member of that group. i would like to ask you how is it calculate the last column (nitrite in mcg) in the last column of the slide you share in January 2023 ( Dr. Urquhart in nitrosamine workshop [nitrite in excipient]). When I multiply the amount of the substance (for instance lactose - 70 mg) per the amount of nitrite (1.7 ppm), then divide by 1000 (to get mcg unit) it gives me 0.12 however in 300 mg (daily dose) noy in 50 mg one tablet. What am I doing wrong? Please help. Krystyna

[Yosukemino]

Thank you for asking, Krystyna. One tablet contains 50 mg of API, and a daily dose of 300 mg requires six tablets with 50 mg of API. The daily dose of a drug is calculated from the amount of API.

It seems to reflect the real case and the total weight of a tablet is confusing because it is the same as the daily dose. It is easy to understand when you focus on the number of tablets to be taken. If you need further help, do not hesitate to ask.

Yosuke

[krystynakk]

Dear Yosuke thank you for the quick answer, however, I do not still understand - why in the first column of the GSK example which should reflect the amount of API in one tablet you have 70 mg of API ? It doesn’t make any sense for one tablet (=50 mg of API) and for 6 tablets (=300 mg API)

[Yosukemino]

I heard the API is in salt form. 50 mg of API is the same as 70 mg of API salt. It is confusing but it is the rule to describe the amounts of total active ingredient as daily dose.

[krystynakk]

ok, now it looks clear - thank you for the explanation