Nitrosamine Reference Standards
Nitrosamines are described in the International Conference for Harmonization (ICH) M7(R1) Guideline 5 as Class 1 impurities which are high-potency, mutagenic. They have been studied for many years due to their presence in foods, cosmetics, tobacco products, industrial solvents, and alcoholic beverages. National Toxicology Program in the 14th Report on Carcinogens published the detail of the toxicity associated with nitrosamines. Exposure to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) is known to produce benign and malignant tumors in variety of nonclinical species. In mid-2018, the regulatory authorities became aware of the presence of N-nitrosamines in sartan active pharmaceutical ingredients (APIs) and more specifically in valsartan. A regulatory action was instituted, including recalls of some medicines from pharmacies and measures to prohibit the use of APIs from certain manufacturers. European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) issued guidance to sartan manufacturers and established limits for sartans. Now nitrosamines have also been found in several products which are not of the sartan class of drugs eg pioglitazone, ranitidine, nizatidine, metformin. As a result, the FDA and EMA are requiring a risk evaluation and appropriate testing of nitrosamine impurities in all marketed products. Several methods have been developed to detect and monitor the amounts of these impurities in the pharma products. Reference standards that are pure, reliable and can be used for quantitative analysis are required for testing. Axios is supporting the pharma industry by providing these reference standards that are fully characterized with a detailed certificate of analysis.