Nitrosamine Impurities in Pharmaceuticals – An Awareness to enhance its Sustainability
Year: 2024
Type: article
Abstract: The N-Nitrosoamines are the concerning class of genotoxic impurities with higher mutagenic potency that leads to carcinogenesis. These impurities are found in different types of Active pharmaceutical ingredients (APIs) and formulations were reminiscing from the market as soon as they were assessed. The present review represents the formation of nitrosamines by nitrosation reaction. Nitrosamines were classified into three groups according to their carcinogenic potential. The bioactivation of nitrosamines were undergone by two mechanisms i.e., by α- hydroxylation and by Cytochrome P450 Monooxygenase pathway. The methyldiazonium ion and formaldehyde, two reactive intermediates of nitrosamines alkylate the DNA to mutate it. The Acceptable intake (AI) was established with the help of the International Council for Harmonization (ICH) M7 (R1) guideline, using Tumorigenic dose 50 (TD50) data with substance specific animal carcinogenicity data and using Carcinogenic potency categorization approach (CPCA) with no substance specific data. The CPCA approach establishes the five different categories and related specified AI limits for Nitrosamine Drug Substance Related Impurities (NDSRI’s). To make drug and drug products sustainable, there is a need to bypass the threat of API scarcities or absolute loss of medicinal choices due to impurities like N-nitrosamines, which requires cooperation of Regulatory Authorities with Pharmaceutical industries is of greater importance to prevent economical as well as resources deprivation. Green synthesis of APIs by replacing the use of nitrating reagents with other most suitable green reagents might prevent the formation of nitrosamine impurities.
Authors: Patil, Vishal, BHAWAL, SUMIT, Patil, Vaishali
Institutions: Navrachana University, Parul University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6949898976
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