Determination of N-nitrosamines in pharmaceuticals, cosmetics and raw material

• Grant number: 21/03239-0
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2021 - July 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Susanne Rath
• Grantee: Susanne Rath
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Paulo César Pires Rosa

Abstract

N-nitrosamines are N-nitrous compounds, considered potent carcinogens for humans, which can be present in a wide variety of products such as food, water, cosmetics, pesticides, medicines and, among others, in environmental samples. The presence of N-nitrosamines in industrialized products needs to be controlled to minimize the risks of consumer exposure. One of the first reports of the presence of N-nitrosamines in pharmaceuticals occurred in the 1970s and, in 2018, again became a worldwide concern since they were detected in several drugs. Among these drugs, the angiotensin II receptor antagonists, known as sartans, were of most concern. These pharmaceuticals are widely used in hypertonia, congestive heart failure, myocardial infarct. In the same way, in recent years the cosmetic industry has also been subject to demands to control the level and prevent the presence of N-nitrosamines in the raw material and in the final product. There are many questions at which stage of the process, contamination occurs. To study the possible sources of contamination in industrial processes, it is necessary to have multi-residue analytical methods of N-nitrosamines that quantify a wide variety of compounds with different polarities in low concentrations and complex and diverse matrices, which is still a significant challenge for scientists. Therefore, the current project's main objective is to develop and validate analytical methods using multidimension liquid chromatography (with heart-cut) associated with tandem mass spectrometry (LC-UHPLC-MS/MS) to evaluate the formation and contamination of medicines, cosmetics, and raw materials by N-nitrosamines. The project also aims to assess the nitrocellulose production process from cellulose nitration and identify possible sources of contamination by N-nitrosamines. Nitrocellulose is a raw material for cosmetic products and an important export product from Brazil. Finally, the samples' analysis should outline a scenario about the contamination of medicines, cosmetics, and raw materials by N-nitrosamines, identifying the main molecules and the concentration levels. These results will be essential to mitigate the contamination of products and minimize the risk of consumers exposure. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE SOUZA, GABRIELA FREITAS PEREIRA; MATOS, MARIA FERNANDA ARAUJO VIEIRA; AGLIO, THARCILLA DE CASTRO; SALLES, AIRTON GONSALVES; RATH, SUSANNE. A comprehensive LC-UHPLC-MS/MS method for the monitoring of N-nitrosamines in lipophilic drugs: A case study with rifampicin. Journal of Pharmaceutical and Biomedical Analysis, v. 236, p. 8-pg., 2023-11-30. (14/50951-4, 21/03239-0)