西格列汀相关亚硝胺杂质(nttp)的ai值 - AI value of sitagliptin related impurity

Limits of Nitrosamines
1

我注意到最近FDA和EMA将西格列汀相关亚硝胺杂质(NTTP)的AI值从37 ng/day更改为100 ng/day，请问之前将NTTP的AI值定为37 ng/day的依据是什么，又为什么改为100 ng/day？

2

Hi,
The AI of 37ng/day had been established applying the SAR approach using the structural surrogate NTPH (TD50=37ug/kg/day). Last year, EMA published an approach for assigning an N-nitrosamine impurity (including nitrosamine drug substance-related impurities [NDSRIs]) to a predicted carcinogenic potency category, with a corresponding acceptable intake (AI) limit, based on an assessment of activating or deactivating structural features present in the molecule, also known as Carcinogenic Potency Categorization Approach (CPCA). Thus, according to CPCA, NTTP belongs to Category 2 and therefore, a higher AI of 100 ng/day established.

hope it helps

5 Likes
3

Thank you very much！

2 Likes