EC Pharmacology and Toxicology

Recently, several pharmaceutical ingredients have been found to contain nitrosamines as impurities, either in the final product or in the active pharmaceutical ingredient (API) itself. Nitrosamines are highly toxic compounds and can produce cancer, as a result, the contaminated active substances were recalled. This situation poses a significant problem, primarily for patients, as it disrupts the supply chain.

A secondary issue is the need to manufacture more nitrosamine-free pharmaceutical ingredients. In this context, it is essential to understand the factors that can lead to the formation of nitrosamines through amine oxidation. These factors include pH, the presence of amines, and nitrosating agents collectively referred to as the "nitrosating triangle". To prevent nitrosamine formation, at least one of these variables must be eliminated during the manufacturing process.

This document presents a perspective on nitrosamine formation in sartans, the degradation of amines, fundamental aspects of analytical development, and general measures to prevent nitrosamine formation in APIs.

 Keywords: Pharmaceutical Ingredient; Impurities; Nitrosamines; Nitrosamine Triangle; Analysis; Control

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