Vikram Hemanth P R, Kumar Tegginamath Pramod, Kumar Gunjan, Beeraka Narasimha M, Deka Rajashree, Suhail Sheik Mohammed, Jat Sandeep, Bannimath Namitha, Padmanabhan Gayatiri, Chandan Ravandur S, Kumar Pramod, Gurupadayya Bannimath
Department of Pharmaceutical Chemistry, JSS College of Pharmacy Mysuru, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, 570015, India.
Xenone Healthcare Pvt. Ltd., New Delhi, 110076, India.
J Pharm Anal. 2024 May;14(5):100919. doi: 10.1016/j.jpha.2023.12.009. Epub 2023 Dec 12.
The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of -nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
药品中存在的亚硝基化合物，尤其是亚硝胺，由于其显著的遗传毒性和致突变作用，引发了全球范围内的安全担忧。本系统综述研究了它们在活性药物成分（API）、药品和药用辅料中的毒性，以及亚硝胺的新型检测分析策略、根本原因分析、重新配方策略和监管指南。本综述强调了亚硝基化合物的分子毒性，重点关注遗传毒性、致突变性、致癌性和其他生理效应。此外，它还探讨了当前的亚硝胺危机、无亚硝胺产品的开发，以及灵敏检测方法和精确风险评估的重要性。这一全面概述将有助于分子生物学家、分析科学家、研发部门的制剂科学家，以及参与亚硝胺诱导毒性管理和推广更安全药品的研究人员。
