A Review on Carcinogenic Impurities Found in Marketed Drugs and Strategies for its Determination by Analytical Methods

Abstract

The control of potentially mutagenic and carcinogenic impurities in pharmaceutical products is key importance in evaluating carcinogenic risk to humans. The recent discovery of nitrosamine impurities in some marketed pharmaceuticals has increased the risk of their mutagenic and carcinogenic potential. According to the International Agency for Research on Cancer (IARC), nitrosamine is the chemical classified as a probable human carcinogen. Nitrosamine impurities are known to be mutagenic and carcinogenic, very small exposure of these impurities can lead to cancer. These impurities may be produced and get incorporated into drug substances or drug products by a reagent, catalyst, solvent, or raw materials used in the process of manufacturing. The presence of nitrosamine impurities in angiotensin II receptor blocker (ARB) drugs containing tetrazole ring has caused worldwide product recalls. The various regulatory authorities have published the press release or notice regarding the control of these impurities with the interim limit. In 2007, the European medicines agency (EMA) suspended the marketing authorization of Viracept, because of the presence of elevated levels of ethyl methane sulfonate, in the drug product. Validated analytical methods are used to identify and quantify these impurities to the trace level at a given interim limit.