Author(s): Ashok B. Patel, Ashish H. Asnani, Amitkumar J. Vyas, Nilesh K. Patel, Ajay I. Patel, Arvind N. Lumbhani

Email(s): asnaniashish7@gmail.com

DOI: 10.52711/2231-5691.2021.00034   

Address: Dr. Ashok B. Patel1, Ashish H. Asnani1*, Dr. Amitkumar J. Vyas1, Dr. Nilesh K. Patel1, Dr. Ajay I. Patel1, Dr. Arvind N. Lumbhani2
1Department of Pharmaceutical Quality Assurance, B.K. Mody Government Pharmacy College Polytechnic Campus, Near Aji dem, Bhavnagar Road, Rajkot - 360003 Gujarat, India.
2Gyanmanjari Pharmacy College, Survey No. 30, Sidsar Road Near Iscon Eleven, Bhavnagar – 364001 Gujarat, India.
*Corresponding Author

Published In:   Volume - 11,      Issue - 3,     Year - 2021


ABSTRACT:
Genotoxic impurities (GTIs) in pharmaceuticals are increasing concern to pharmaceutical industries due to their potential for human carcinogenicity. The literature currently lacks the Guidance for the analytical determination of diverse classes of GTIs. This review article provides brief information regarding Genotoxic impurity (GTI), its sources, their classification, and existing regulatory approaches to control Genotoxic impurities in Pharmaceuticals, also information regarding different types of GTI and examples of each class. It is very difficult for researchers to detect GTI at Trace level so the detection method is also given in the chart, almost all the GTI are Mutagenic but as shown in Nitrosamines it is Mutagenic and its carcinogenicity is also proved but there are no such strong evidence and literature which shows genotoxicity. So, it is included as Mutagenic & carcinogenic. Different Control strategies to control Genotoxicity are also discussed.


Cite this article:
Ashok B. Patel, Ashish H. Asnani, Amitkumar J. Vyas, Nilesh K. Patel, Ajay I. Patel, Arvind N. Lumbhani. A Brief Review on Genotoxic impurities in Pharmaceuticals. Asian Journal of Pharmaceutical Research. 2021; 11(3):187-3. doi: 10.52711/2231-5691.2021.00034

Cite(Electronic):
Ashok B. Patel, Ashish H. Asnani, Amitkumar J. Vyas, Nilesh K. Patel, Ajay I. Patel, Arvind N. Lumbhani. A Brief Review on Genotoxic impurities in Pharmaceuticals. Asian Journal of Pharmaceutical Research. 2021; 11(3):187-3. doi: 10.52711/2231-5691.2021.00034   Available on: https://asianjpr.com/AbstractView.aspx?PID=2021-11-3-8


REFERENCES:
1.     Parajuli RR et al. Impurity Profiling : An Emerging Approach for Pharmaceuticals. World Journal Of Pharmacy And Pharmaceutical Sciences. 2018; 7(4): 1670–83.
2.     ICH. ICH S2 (R1) - Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for Human Use. Int Conf Harmon. 2011; 2(November): 29. Available on: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S2_R1/Step4/S2R1_Step4.pdf
3.    Ahamed Noor Mansoori, Rupesh K. Gautam, Prafulla C. Tiwari. A Review on Genotoxicity. Asian J. Pharm. Res. 4(3): July-Sept. 2014; Page 162-165.
4.    S Selvaraju, M Vasanth, R Rajarajan, R Muralidharan, V Raghupathy. Genotoxic Effects of Carbendezim (fungicide) on the Root Apicalmeristems of Allium cepa L. Res. J. Pharmacognosy & Phytochem. 2015; 7(1): 29-33.
5.    Mahmood Kahtan, Ali Faris Hassan, Nada Naje Al-Shawi, Intesar Tareq Numan, Ghaith Abbas Bahader. The Genoprotective Activity of Aqueous Green Tea extract against Metronidazole and Tinidazole Genotoxic Effect. Research J. Pharm. and Tech 2020; 13(2):889-894.
6.     Reddy AVB et al. Identification, control strategies, and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review. The Journal of Separation Science. 2015; 38(5): 764–79.
7.     Acree W. Toxicity and Drug Testing. Janeza Trdine, Croatia.2012.
8.    Dhara Vashi, Suresh Kumar. Impurity Identification and Characterization of some Anti-Diabetic Drugs using various Analytical Methods. Asian J. Pharm. Res. 2019; 9(4):243-248.
9.    O.S.S. Chandana, R. Ravichandra Babu. Stability Indicating HPLC Method Development and Validation for Thalidomide and its Impurity Determination. Asian J. Pharm. Ana. 2016; 6(2): 115-118.
10.    D. Benito Johnson, Sai Kishore P., M. Adarsh Verma, Tamil Selvan. A. Antimutagenic Activity of Terminalia chebula Fruit Extract. Research J. Pharmacognosy and Phytochemistry 2010; 2(6): 455-459.
11.    Pushpa Prasad, R.C. Agrawal, Amit Roy, Nirmala Gupta. Antimutagenic effects of Tribulus terristris fruit extract on Micronucleus. Research J. Science and Tech. 2012; 4(3):140-142.
12.     Pounikar A et al. Genotoxic Impurities: An Important Regulatory Aspect. Asian Journal of Pharmaceutical and  Clinical  Research. 2010; 13 (6): 10-25.
13.     Haney BP et al. Controlling the Genotoxins Ethyl Chloride and Methyl Chloride Formed during the Preparation of Amine Hydrochloride Salts from Solutions of Ethanol and Methanol. Organic Process Research and  Development. 2009; 13 (4): 786-791.
14.     Fleming NW, Henderson TR, Dretchen KL. Mechanisms of respiratory failure produced by neostigmine and diisopropyl fluorophosphate. Europian Journal of Pharmacology. 1991; 195: 85–91.
15.     Benigni R and Bossa C. Mechanisms of chemical carcinogenicity and mutagenicity: A review with implications for predictive toxicology. Chem Reviews. 2011; 111 (4): 2507–36.
16.     Kovacic P and Jacintho JD. Mechanisms of Carcinogenesis: Focus on Oxidative Stress and Electron Transfer. Current medicinal chemistry. 2001; 8 (7): 773-796.
17.     Terrett NK et al. Sildenafil (Viagra(TM)), a potent and selective inhibitor of type 5 CGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorganic and  Medical Chemistry Letter. 1996; 6 (15): 1819–1824.
18.     Szekely G et al. Genotoxic impurities in pharmaceutical manufacturing: Sources, regulations, and mitigation. Chem Reviews. 2015; 115 (16): 8182–8229.
19.     Jackson RJ et al. Oseltamivir, zanamivir and amantadine in the prevention of influenza: A systematic review. Journal of  Infection. 2011; 62 (1): 14–25.
20.     Snodin DJ. Genotoxic impurities: From structural alerts to qualification. Organic Process Research and Development. 2010; 14 (4): 960–976.
21.     O’Donovan MR et al. Boronic acids-A novel class of bacterial mutagen. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2011; 724 (1–2): 1–6.
22.     Gocke E at al. Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate. Toxicological Letters. 2009; 190 (3): 254–265.
23.     Ghosh AK, Bilcer G, Schiltz G. Syntheses of FDA approved HIV protease inhibitors. Synthesis (Stuttg). 2001; (15): 2203–2229.
24.     European Medicines Agency. Lessons learnt from presence of N-nitrosamine impurities in sartan medicines. Available on: https://www.ema.europa.eu/en/documents/report/lessons-learnt-presence-n-nitrosamine-impurities-sartan-medicines_en.pdf
25.     Shaikh T, Gosar A, Sayyed H. Nitrosamine Impurities in Drug Substances and Drug Products. Journal of Advances in Pharmacy Practices. 2019; 2 (1): 48–57.
26.     Raman NVVSS, Prasad AVSS, Ratnakar Reddy K. Strategies for the identification, control and determination of genotoxic impurities in drug substances: A pharmaceutical industry perspective. Journal of Pharmaceutical and Biomedical Analysis. 2010; 55 (4): 662–667.
27.    M. Yogeshwar Reddy, V. Ramesh, Ch. Kista Reddy, N. Venugopal, G. Saravanana, M.V. Suryanarayana, B. Shyam Sunder, R. Surendranath Reddy, G. Raju. The Quantitative Determination of Process Related Genotoxic Impurities in Esomeprazole Magnesium by GC-MS. Asian J. Research Chem. 4(6): June 2011; Page 898-901.
28.    Tabassum H. Aaraf, Hasumati A. Raj, Vineet C. Jain, Vishnu Sutariya. Development and Validation of Ratio derivative Spectrophotometric Method for Estimation of Metronidazole Benzoate and related Impurity in Bulk and Pharmaceutical Formulation. Asian J. Pharm. Tech. 2015; Vol. 5: Issue 2, Pg 66-70.
29.    Maitry Desai, Mukesh Gupta. Method Development and Validation using RP-HPLC for estimation of Genotoxic impurity i.e. Melamine mainly present as contaminant in diversified categories of API. Asian J. Research Chem. 2017; 10(4):491-496.

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