Development of analytical methods by high performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS) for detection and quantification of nitrosamines in drugs widely used by the Brazilian population

• Grant number: 22/03919-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2022
• End date: May 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Rodrigo Moreira da Silva
• Grantee: Luiz Ricardo Penariol Fabri
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In recent years, a class of compounds called nitrosamines, which are impurities known for their carcinogenic potential has been found in antihypertensive drugs, antidiabetics, drugs used to treat gastritis and gastric ulcers, and antibiotics. In July 2021, the National Health Surveillance Agency (ANVISA) published the Guide on the Control of Nitrosamines in Active Pharmaceutical Ingredients and Medicines, which establishes that the control of nitrosamines must go through three steps described in accordance with the risk management principles of the ICH Guide Q9 - Quality Risk Management (ICH 2005). The second of these three steps consists of carrying out confirmatory tests, using sensitive and validated analytical methods for the detection and quantification of nitrosamines. Thus, considering the strong specialized demand for this step 2 required by health agencies, the present project aims to develop analytical methods using high-performance liquid chromatography coupled with mass spectrometry for the detection and quantification of nitrosamines that can be applied in the confirmatory analysis of pharmaceutical products. It is expected that the methods developed in this project can be used as models for the pharmaceutical industries in the stages of sample preparation, chromatographic separation parameters, detection, and quantification of nitrosamines in finished products. In addition, provide subsidies to accelerate the confirmation of toxicological risks due to the possible formation of nitrosamines in medicines.(AU)