🇪🇺 EMA Q&A Rev. 16 EMA/409815/2020 - MAJOR UPDATE

that is I believe the structure - it’s not nitroso-sitagliptin itself, rather the nitrosamine of an impurity of sitagliptin.

It has been assigned a compound-specific limit of 37 ng/day by read-across from nitroso-1,2,3,6-tetrahydropyridine (with the aromatic group assumed to be comparable to the double bond there and the ‘arylic’ position like the allylic in NTHP), though by CPCA would have a limit of 100:

(2,2) for H-count = 1
In a generic 6-membered ring = 2
Aromatic group at b-position activating it = -1
Total 2, limit 100 ng/day

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