Reports a couple of years ago indicated the presence of NDMA in macrocyclic antibiotics such as Spiramycine, more recently concerns over the associated NDSRI. Was the presence of NDMA ever fully disclosed? Also has any evidence of presence of the NDSRI been reported?
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Dear Andy,
in the EMA appendix 1, there are three nitrosamines listed which are correlated with macrolides,
N-nitrosodesmethylazithromycin, N-nitrosoazaerithromycin and N-nitrosodesmethylclarithromycin. The first two has been charactarized as NMI (through in-vivo study). The same charactarization has been given also for the nitrosamine of clarithromycine but through read-across and weight of evidence approaches based on the N-nitrosodesmethylclarithromycin. Actually, as it has been reported in this forum before some time, this could be the beginning of setting AI limits for whole category of compounds using the in-vivo data of a representative surrogate.
regards,
Christos
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The only thing that I can immediately think of is the acetylspiramycin inclusion in a nitrosation experiment in https://doi.org/10.1021/acs.chemrestox.4c00435:
“While it is unclear which amine group in Acetylspiramycin releases NDMA, it was not excluded from the dataset since the yield of 0.005% is approximated to be zero.” (see last SI file).
| (Q)SAR Approaches to Predict the Extent of Nitrosation in Pharmaceutical Compounds | Chemical Research in Toxicology |
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