Hi David,
I confirm that the limit of 5 ppm for (2RS)-2-methyl-1-nitroso-2,3-dihydro-1H-indole (impurity A) has been already present in Indapamide monograph since Jan.2008 (or even before).
Therefore, this limit was stated well before the “nitrosamine saga” and probably it was stated taking in account the sensitivity of the Ph.Eur. method (UV-HPLC).
Other cases of “legacy limits” of nitrosamine impurities are:
- 2-nitroso-octahydrocyclopenta [c] pyrrole (impurity B of Glicazide) NMT 2 ppm
- N-nitrosodiethanolamine [impurity C of Trolamine (Triethanolamine)] NMT 24 ppb
No rationale can be found on these limits.