Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications, root causes and risk assessment: A systematic review

Hemanth P. R. Vikram; Tegginamath Pramod Kumar; Gunjan Kumar; Narasimha M. Beeraka; Rajashree Deka; Sheik Mohammed Suhail; Sandeep Jat; Namitha Bannimath; Gayatiri Padmanabhan; Ravandur S. Chandan; Pramod Kumar; Bannimath Gurupadayya

doi:10.1016/j.jpha.2023.12.009

Volume 14 Issue 5

May 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(5): 100919

Hemanth P. R. Vikram, Tegginamath Pramod Kumar, Gunjan Kumar, Narasimha M. Beeraka, Rajashree Deka, Sheik Mohammed Suhail, Sandeep Jat, Namitha Bannimath, Gayatiri Padmanabhan, Ravandur S. Chandan, Pramod Kumar, Bannimath Gurupadayya. Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications, root causes and risk assessment: A systematic review[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100919. doi: 10.1016/j.jpha.2023.12.009

Citation:

Hemanth P. R. Vikram, Tegginamath Pramod Kumar, Gunjan Kumar, Narasimha M. Beeraka, Rajashree Deka, Sheik Mohammed Suhail, Sandeep Jat, Namitha Bannimath, Gayatiri Padmanabhan, Ravandur S. Chandan, Pramod Kumar, Bannimath Gurupadayya. Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications, root causes and risk assessment: A systematic review[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100919. doi: 10.1016/j.jpha.2023.12.009

Citation:

Hemanth P. R. Vikram, Tegginamath Pramod Kumar, Gunjan Kumar, Narasimha M. Beeraka, Rajashree Deka, Sheik Mohammed Suhail, Sandeep Jat, Namitha Bannimath, Gayatiri Padmanabhan, Ravandur S. Chandan, Pramod Kumar, Bannimath Gurupadayya. Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications, root causes and risk assessment: A systematic review[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100919. doi: 10.1016/j.jpha.2023.12.009

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Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications, root causes and risk assessment: A systematic review

doi: 10.1016/j.jpha.2023.12.009

a. Department of Pharmaceutical Chemistry, JSS College of Pharmacy Mysuru, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, 570015, India;
b. Xenone Healthcare Pvt. Ltd., New Delhi, 110076, India;
c. Department of Pharmaceutics, JSS College of Pharmacy Mysuru, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, 570015, India;
d. Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991, Russian Federation;
e. Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Ananthapuramu, 515721, India;
f. Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA;
g. Animal Physiology and Biochemistry Laboratory, Department of Zoology, Gauhati University, Guwahati, 781014, India;
h. Department of Pharmacology, JSS College of Pharmacy Mysuru, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, 570015, India;
i. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, India;
j. Department of Pharmacology, University of Galway, Galway, H91 TK33, Ireland

Funds:

The authors would like to express their heartfelt gratitude to Shri Gunjan Kumar, Director of Xenone Healthcare Pvt. Ltd, New Delhi, and JSS Academy of Higher Education and Research (JSSAHER), India for unwavering support during the entire work and SERB-CII Prime Minister Fellowship, Government of India for the fellowship awarded to Mr. Hemanth P.R. Vikram.

Received Date: Jul. 05, 2023
Accepted Date: Dec. 08, 2023
Rev Recd Date: Dec. 02, 2023
Publish Date: May 30, 2024

Abstract

Abstract

The presence of N-nitroso compounds, particularly N-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 N-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.
- Carcinogenicity,
- Genotoxicity,
- Mutagenicity,
- Molecular toxicity,
- Nitrosamine impurities,
- Nitrosamine drug substance-related impurities

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References(190)

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