Take Control of Nitrosamine Impurities

The impurity N-nitrosodimethylamine (NDMA) was first detected in Sartans (e.g. Valsartan). The “Sartan” family is typically used for the treatment of blood pressure and if it is used over a long period can eventually expose the patients to carcinogenicity effects even in trace amounts. In 2019, much like Sartans, NDMA was detected in Ranitidine, a proton pump inhibitor to treat acid reflux.

Potential dangers on exposure

The International Agency for Research on Cancer has classified NDMA as a probable carcinogen, with animal studies finding tumor formation predominantly in the gastrointestinal tract and liver but also in the lungs and kidneys.

NDMA in Valsartan and Ranitidine- How are they different?

NDMA was found to be present not only in Valsartan but also in Ranitidine, as an impurity. However, in Ranitidine, it was found to have formed as a part of reaction under high temperatures typically used in GC/MS (Gas chromatography/Mass Spectrometry) technology. USFDA, thereby, suggests GC/MS as the ideal analytical technique for Sartan compounds while LC/MS/MS for Ranitidine.

The control measures

Impurities in Sartan compounds, as mentioned above, are a result of the manufacturing process. Sources could be different ranging from raw materials or solvents to contaminated equipment. Hence, the responsibility resides with the API manufacturers to control and remove the impurities during the manufacturing process itself. This will give rise to more stringent regulations at the manufacturing level which will eventually pave the way to more quality products.

At the analytical level, advanced technologies like PerkinElmer’s QSight^® LC-MS/MS or Clarus GC/MS with TurboMatrix Headspace have taken sensitivity capabilities to new levels with an emphasis on faster analysis time with negligible instrument breakdown and very high throughput.

The Future Scenario

The regulatory bodies are being constantly reminded that the carcinogenic or the possible side effects of NDMA express differently in different people. This calls for tighter stringent review and testing for any new drug approvals at the manufacturing level.

Considering the technological advancements, we see today, Pharma companies will be forced to invest in next-gen. analytical equipment that can generate seamless and reproducible results faster than ever.

To learn more about our solutions please visit https://www.perkinelmer.com/category/control-of-impurities

For more updates from FDA: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine