Which limit to be consider the limit for N-nitroso Vortioxetine ? 1.3 ppm per day or 0.9 ppm per day ?

The maximum daily dose of drug substance is 20 mg.

Hi! Would you mind sharing with us why 1.3 and why 0.9 first, so we can give some input. Aas 2 differents proposals means two different surrogates has been considered.

Considering 26 ppm as limit we get 1.3 ppm per day value.

As per SAR calculations, it will get 0.9 ppm

For N-nitroso-vortioxetine you can use general limit of 18 ng/day which result in a limit of 0.9 ppm.

Using SARS approach it is possible derivate the limit based in others nitrosamines, like NDEA with limit of 26.5 ng/day which result in a limit of 1.3 ppm

I suggest, to correlate N-nitroso-vortioxetine with others nitrosamines like 1-Nitrosopiperazine (TD50 6.04 mg/kg/day) or 1,2,6-Trimethyl-4-nitrosopiperazine (TD50 0.153 mg/kg/day), thus is possible to achieve higher values like 302.00 ppm ( limit derivated from 1-Nitrosopiperazine) or 7,65 ppm (limit derivated from 1,2,6-Trimethyl-4-nitrosopiperazine).