Apotex recalls additional Apo-Acyclovir tablets due to a nitrosamine impurity

Nitrosamines in the News
4

Hi Nilesh,

Sorry for getting involved. Regarding the amine topic I highly suggest you to read this paper and if not yet the whole thread by Yosukemino References in Nitrosamines Exchange - About Nitrosamines Exchange - Nitrosamines Exchange (usp.org):

Potential for the Formation of N-Nitrosamines during the Manufacture of Active Pharmaceutical Ingredients: An Assessment of the Risk Posed by Trace Nitrite in Water | Organic Process Research & Development (acs.org)

It is well known that secondary amines are several times fold more prone to nitrosation that tertiary amines.

Regarding the aciclovir topic, this kind of products I think are OTC in Canada. Thus it should be a very old marketing authorization as aciclovir is an old molecule. What you are mentioning is to launch of new products. This specific one seems to be from late 90s and revised in 2014. By that time of release there was no clear information or any regulatory enforcement about N-N=0s.

In particular I have seen in the synthesis of the API that triethylamine is used as a solvent that can contain traces of diethylamine (up to 500 ppm as per manuf. spec.). Also, I have seen nitrous acid used in the process in some route of synthesis. So this could be one of the root causes for NDEA formation instead of NDMA. I am not sure if triethylamine can contain traces of dimethylamine. So the DMF theory makes sense unless more details are known.

1 Like