In 2018, the detection of N-Nitroso-N,N-dimethylamine (NDMA) in Valsartan, a medication used for blood pressure control, and subsequent similar observations in products containing Losartan, Ranitidine, and Metformin, led to a temporary limited availability of medicines worldwide and initiated a comprehensive risk assessment campaign for all human medicines containing chemically synthesized active pharmaceutical ingredients (APIs).
The scope of risk assessment and the numerous underlying causes of contamination make the need for robust and reliable determination of nitrosamine content in various matrix types urgent. To contribute to patient safety and support the pharmaceutical industry, Novagenix has decided to develop a versatile, proprietary LC/MS/MS method for the quantitative determination of nitrosamines.
The method is based on an isotopic-labeled internal standard and is inspired by methods published by regulatory bodies. Minor changes in parameters and/or sample preparation allow the method to be adapted to specific matrices. The method has been successfully applied to APIs, solid dosage forms, infusion solutions, oral solutions, semi-finished products, or excipients using a Waters Andrew pipetting robot.
Our experience extends far beyond the determination of N-Nitroso-N,N-dimethylamine (NDMA), and to date we have practical experience with eight nitrosamines, including nitrosamine analogs; this confirms the versatility of the method. LOQ values have been studied at single-digit ppb levels by lowering the defined intermediate limits for the maximum daily intake.