In 2018 authorities recalled off the market a group of angiotensin II receptor blockers – sartans, due to NDMA (N-nitroso dimethylamine) impurity presence. That was the first step to analyse drug products against nitrosamines impurities and it has been thoroughly investigated ever since.
Nitrosamines impurities come from carcinogens family, which are formed in reaction of amides, secondary amines, urea derivatives. carbamates and other nitrogenous agents with nitrogen atom in +3 state. They are Class 1 impurities by the ICH M7(R1) Guideline and several root causes of their presence in pharmaceutical products has been identified:
- Contaminated raw materials in API production
- Use of nitrosating agents and recovered materials
- Nitrosamines contaminated starting materials and intermediates
- Specific packaging materials and degradation processes
As result, EMA requested marketing authorization holders to review drug products containing synthetized APIs against nitrosamines impurities content.
Selvita is prepared to support Clients throughout the testing process of method development, cGMP validation and routine batch analysis. Our team is experienced in working with very low impurities levels, which is characteristic for nitrosamines detection, as well as challenging matrixes.
- NDMA, NDEA testing in valsartans, using HS-GC-MS
- NDMA testing in ranitidine, using LC-HRMS; LC-MS/MS
- NDMA, NDEA, NEIPA, NDIPA, NDBA, NMBA testing in losartan potassium, using LC-HRMS