Development of a General Pharmacopoeial Monograph for Determining the Content of N-Nitrosoamine Impurities in Pharmaceutical Substances of the Sartan Group and Metformin Substances for Inclusion in the State Pharmacopoeia

A large volume of information has been accumulated in recent years on the detection of N-nitrosamines, which can be formed in objects and living organisms from a large range of nitrogen-containing and nitrosating substances. There are more than 300 such compounds, about 90% of which are carcinogenic. The development of highly sensitive chromatographic methods for the quantitative determination of these compounds, GC-MS and HPLC-MS, which enable the determination of nanogram traces of N-nitrosamines, played an important role in the study of N-nitrosamines. The Institute of Pharmacopoeia and Standardization in the Sphere of Circulation of Medicines of the Federal State Budgetary Institution “Scientific Center for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation together with the Yaroslavl branch of the Federal State Budgetary Institution “Information and Methodological Center for Expertise, Accounting and Analysis of Circulation of Medicinal Products” of Roszdravnadzor developed a draft general pharmacopoeial monograph (GPM) “Determination of impurities of N-nitrosamines”. The developed GPM includes validated methods (GC-MS, HPLC-MS) applicable for the quality control of synthetic pharmaceutical substances of the sartan group and metformin substances in laboratories with different equipment.