55.Issue 07 july 22 - INDO AMERICAN JOURNAL OF PHARMACEUTICAL SCIENCES

Volume : 09, Issue : 07, July – 2022

Title:

55.METHOD DEVELOPMENT AND VALIDATION OF FIVE NITROSAMINES IMPURITIES CONTENT IN TELMISARTAN DRUG SUBSTANCE BY GC-MS/MS
‬

Authors :

*Harendra Singh, * Dr. Rahul Kumar

Abstract :

A proficient GC-MS/MSS method was developed for determination of N-Nitrosodimethylamine, N-Nitrosodiethylamine, N-Nitrosodiisopropylamine, N-Nitrosoisopropylethylamine, N-Nitrosodibutylamine impurities in Telmisartan Drug Substance using column Rtx-5 Amine (30m length X 0.32mm diameter) 1.5µm film thickness, Part No.: 12369, Make: Restek. Helium is used as Carrier gas at with Linear velocity of 44.3 cm/sec. The proposed method was validated for System suitability, Specificity, Linearity, LOD and LOQ, Method precision, Intermediate precision and Recovery. All the parameters were found within the acceptable limits. Linearity in the range of LOQ to 150% for each impurity. The established methodology was commercially useful, specific, accurate, precise and suitable for the analysis of Nitrosamines impurities in Telmisartan drug substance
Keywords: Gas chromatography with mass spectrometry (GC-MS/MS), Telmisartan drug substance, Nitrosamine impurities, ICH guideline and Method Validation.

Cite This Article:

Please cite this article in press Harendra Singh et al, Method Development and Validation Of Five Nitrosamines Impurities Content In Telmisartan Drug Substance By GC-MS/MS., Indo Am. J. P. Sci, 2022; 09(7).,

Number of Downloads : 10

References:

1. Beard, Jessica C.; Swager, Timothy M. (21 January 2021). “An Organic Chemist’s Guide to N-Nitrosamines: Their Structure, Reactivity, and Role as Contaminants”. The Journal of Organic Chemistry. 86 (3): 2037–2057. doi:10.1021/acs.joc.0c02774. PMID 33474939.
2. Yang, Chung S.; Yoo, Jeong-Sook H.; Ishizaki, Hiroyuki; Hong, Junyan (1990). “Cytochrome P450IIe1: Roles in Nitrosamine Metabolism and Mechanisms of Regulation”. Drug Metabolism Reviews. 22 (2–3): 147–159. doi:10.3109/03602539009041082. PMID 2272285.
3. Anselme, Jean-Pierre (1979). “The Organic Chemistry of N-Nitrosamines: A Brief Review”. N-Nitrosamines. ACS Symposium Series. 101. pp. 1–12. doi:10.1021/bk-1979-0101.ch001. ISBN 0-8412-0503-5.
4. Vogel, A. I. (1962). Practical Organic Chemistry (3rd ed.). Impression. p. 1074.
5. G. Subba Rao (1980), “NNitrosarnines from drugs and nitrite: potential source of chemical carcinogens in humans”, Pharmacy International, Volume 1, pp. 187-190.
6. Hecht, Steven S.; Borukhova, Anna; Carmella, Steven G. “Tobacco specific nitrosamines” Chapter 7; of “Nicotine safety and toxicity” Society for Research on Nicotine and Tobacco; 1998 – 203 pages.
7. Hecht, Stephen S. (1998). “Biochemistry, Biology, and Carcinogenicity of Tobacco-Specific N-Nitrosamines”. Chemical Research in Toxicology. 11 (6): 559–603. doi:10.1021/tx980005y. PMID 9625726
8. Nowak M, Seubert A. Application of experimental design for the characterization of a novel elution system for high-capacity anion chromatography with suppressed conductivity detection. Journal of Chromatography A. 1999;855: 91-109.
9. ICH Q2 (R1) Validation of Analytical Procedures: Definitions and Methodology, Geneva, 2005, in 2005 incorporated in Q2 (R1).
10. Wang Y, Harrison M, Clark B. Optimizing reversed-phase liquid chromatographic separation of an acidic mixture on a monolithic stationary phase with the aid of response surface methodology and experimental design. Journal of Chromatograhy A, 2006;1105: 199-207.
11. Jakszyn, P; Gonzalez, CA (2006). “Nitrosamine and related food intake and gastric and oesophageal cancer risk: A systematic review of the epidemiological evidence”. World Journal of Gastroenterology. 12 (27): 4296–4303. doi:10.3748/wjg.v12.i27.4296. PMC 4087738. PMID 16865769.
12. Combet, E.; Paterson, S; Iijima, K; Winter, J; Mullen, W; Crozier, A; Preston, T; McColl, K. E. (2007). “Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation”. Gut. 56(12): 1678–1684. doi:10.1136/gut.2007.128587. PMC 2095705. PMID 17785370
13. Honikel, Karl-Otto (2008). “The use and control of nitrate and nitrite for the processing of meat products”. Meat Science. 78 (1–2): 68–76. doi:10.1016/j.meatsci.2007.05.030. PMID 22062097.
14. Raj T, Bharathi C, Saravana M, Prabahar J, Kumar P, Sharma H, Parikh K. Identification, isolation and characterization of process – related impurities in Rizatriptan benzoate. Journal of Pharmaceutical and Biomedical Analysis, 2009;49: 156-162.
15. Combet, E; El Mesmari, A; Preston, T; Crozier, A; McColl, K. E. (2010). “Dietary phenolic acids and ascorbic acid: Influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipids”. Free Radical Biology and Medicine. 48 (6): 763–771. doi:10.1016/j.freeradbiomed.2009.12.011. PMID 20026204.
16. Wisler J, Black K, Assessment of genotoxic impurities in small molecule drug candidates. Comparative Biology and Safety Sciences, Amgen Inc., Northern California SOT Meeting, 06-May-2010.
17. ICH M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to limit potential Carcinogenic Risk, Business plan 2010. Position paper 2010.
18. Elder, D.P., Snodin. D., and Teasdale, A Control and Analysis of Hydrazine, Hydrazides, Hydrazones Genotoxic Impurities in Active Pharmaceutical ingredients (APIs) and Drug products. J Pharm Biomed Anal., 2011, 54:900-910.
19. R. Nilsson (July, 2011), “The molecular basis for induction of human cancers by tobacco specific nitrosamines”, Regulatory Toxicology and Pharmacology, Volume 60, Issue 2, pp. 268-80. Available at https://doi.org/10.1016/j.yrtph.2011.02 .014.
20. Joyce I. Boye; Yves Arcand (2012-01-10). Green Technologies in Food Production and Processing. Springer Science & Business Media. p. 573. ISBN 978-1-4614-1586-2
21. Indian Pharmacopoeia, Volume-II, 2014.
22. “Information on nitrosamines for marketing authorization holders”, European Medicines Agency, pp. 1-10, EMA/CHMP/428592/2019 Rev. 2.
23. U. S. Food and Drug Administration (February, 2019), “FDA update table of interim limits for nitrosamine impurities in ARBs”, from https://www.fda.gov.
24. European Medicines Agency (2019), “Temporary interim limits for NMBA, DIPNA and EIPNA impurities in sartan blood pressure medicines”, EMA/351053/2019 rev. 1.
25. Aloka Srinivasan (2019), “Proactive Evaluation of Possible Genotoxic Impurities during the Early Stages of Drug Development”, http://www.pharmtech.com.
26. “EMA to provide guidance on avoiding nitrosamines in human medicines”. European Medicines Agency (EMA) (Press release). 13 September 2019. Retrieved 19 September 2019.
27. Method Development and Validation of 2-[(2-Methoxyphenoxy) Methyl] Oxirane Content In Ranolazine Drug Substance By LC-MS/MS. Journal of Chemistry and Chemical Sciences, Vol.10(12), 377-388, December, 2020.
28. Method Development and Validation of Epichlorohydrin content in Ranolazine drug substance by GC-MS/MS. Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 8(3), 306-316, 2020.
29. Analyzing three Genotoxic impurities of Atorvastatin calcium employing GC-MS single quad detector with electron impact technology. Rasayan J. Chem. Vol. 14, No. 2, 1081-1086, April – June, 2021.
30. Method Development and Validation 0f N, N dimethylaminopropyl Chloride (DMPC) Content in Clomipramine Hydrochloride Drug Substance By GC-MS/MS. Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 9(3), 121-131, 2021.