The European Medicines Agency (EMA) will require companies that make angiotensin II antagonists, commonly known as ‘sartans’, to review their manufacturing processes and prove they do not produce nitrosamine impurities. According to the EMA report[1] impurities can form during the production of sartans that contain a specific ring structure (tetrazole) under certain conditions and when certain solvents, reagents, and other raw materials are used. Companies must now take measures to avoid the presence of these impurities and carry out rigorous testing of their products. Following a two-year transition period, during which strict temporary limits on the levels of these impurities will apply, manufacturers will need to demonstrate that their sartan products have no quantifiable levels of these impurities (< 0.03 parts per million). EMA and national authorities continue investigating the presence of nitrosamine impurities in medicines, including other impurities such as N-nitrosoethylisopropylamine (EIPNA), N-nitrosodiisopropylamine (DIPNA) and N-nitroso-N-methylamino butyric acid (NMBA).
The identification and quantification of impurities in drug products requires a wide range of analytical techniques for structure elucidation and quantification of small molecules, from unknown compounds in release analytics to the development of methods for routine impurities. With more than 20 years of experience in the identification, development and validation of methods for the quantification of impurities, Solvias has developed a portfolio of over 100 methods.
Specifically, Solvias offers expert services in trace analysis of impurities in drug products, providing quantification of nitrosamines at the levels requested by EMA. In addition, Solvias provides a full spectrum of analytical services for controlling genotoxic impurities (GTIs) in line with ICH guideline M7 (R1)[4] for the assessment and control of DNA-reactive or mutagenic impurities in pharmaceuticals to limit potential carcinogenic risk. Our experts offer analytical methods using state-of-the-art equipment such as high-resolution, accurate-mass (HRAM) Orbitrap LC-MS/MS, Liq. Inj. GC-MS/MS, HS-GC-MS/MS. Regardless of the matrix, the genotoxic compound and chemical or physical properties, GTI control relies on careful method selection and know-how born from years of experience.
Would you like to know more about our expert services for the testing of nitrosamines in sartans? For details about our reliable and timely trace analysis of sartans and other impurities, contact Solvias today!
[1] EMA/44960/2019
[2] Valsartan Article 31 referral – Sartan medicines: companies to review manufacturing processes to avoid presence of nitrosamine impurities link
[3] Article 31 of Directive 2001/83/EC
[4] ICH guidelines M7 (R1) link
