12.Issue 08 august 22 - INDO AMERICAN JOURNAL OF PHARMACEUTICAL SCIENCES

Volume : 09, Issue : 08, August – 2022

Title:

12.QUANTITATIVE EVALUATION OF N-NITROSAMINE IMPURITIES IN TELMISARTAN TABLETS USP 20MG, 40MG AND 80MG BY GAS CHROMATOGRAPHY COUPLED WITH MASS SPECTROMETER
‏‬

Authors :

Dr. Rahul Kumar, Rahul Dev, Kunwar Sanjeev Singh, Dr. Anil Tyagi, Hari Darshan Singh, Harendra Singh, Vikash Mohniya and Manish Chouhan

Abstract :

Determination of Nitrosamine Impurities (N-Nitrosodimethylamine, N-Nitrosodiethylamine, N-Nitrosodiisopropylamine, N-Nitrosoisopropylethylamine, N-Nitrosodibutylamine) in Telmisartan Tablets USP 20 mg, 40 mg and 80 mg by GC-MS/MS. Using column Rtx-5 Amine fused silica capillary column with Base deactivated guard column. The validation of optimized method was carried out in accordance with relevant validation principles. The authenticated procedure was noticed to be specific, precise, linear, accurate and rugged with concentration ranging from limit of quantification (LOQ) to 200% specification level for Nitrosamine Impurities. As per daily dose of Telmisartan Tablets, the specification limits of N-Nitrosodimethylamine is 1.2mcg/gm and other Nitrosamine Impurities is 0.33mcg/gm. In this method the limit of detection for N-Nitrosodimethylamine is 0.12mcg/gm and other Nitrosamine Impurities is 0.033mcg/gm. The established method was productively useful to determine the N-Nitrosamine Impurities in Telmisartan Tablets.
Keywords: Gas chromatography coupled with mass spectrometry (GC-MS/MS), Telmisartan tablets USP, Nitrosamine impurities, ICH guideline.

Cite This Article:

Please cite this article in press Rahul Kumar et al, Quantitative Evaluation Of N-Nitrosamine Impurities In Telmisartan Tablets USP 20mg, 40mg And 80mg By Gas Chromatography Coupled With Mass Spectrometer., Indo Am. J. P. Sci, 2022; 09(8).,

Number of Downloads : 10

References:

1. 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
2. ICH Q2 (R1) Validation of Analytical Procedures: Definitions and Methodology, Geneva, 2005, in 2005 incorporated in Q2 (R1).
3. 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.
4. 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.
5. 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
6. 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.
7. 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.
8. 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.
9. 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.
10. ICH M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to limit potential Carcinogenic Risk, Business plan 2010. Position paper 2010.
11. 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.
12. 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.
13. 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
14. Indian Pharmacopoeia, Volume-II, 2014.
15. “Information on nitrosamines for marketing authorization holders”, European Medicines Agency, pp. 1-10, EMA/CHMP/428592/2019 Rev. 2.
16. U. S. Food and Drug Administration (February, 2019), “FDA update table of interim limits for nitrosamine impurities in ARBs”, from https://www.fda.gov.
17. European Medicines Agency (2019), “Temporary interim limits for NMBA, DIPNA and EIPNA impurities in sartan blood pressure medicines”, EMA/351053/2019 rev. 1.
18. Aloka Srinivasan (2019), “Proactive Evaluation of Possible Genotoxic Impurities during the Early Stages of Drug Development”, http://www.pharmtech.com.
19. “EMA to provide guidance on avoiding nitrosamines in human medicines”. European Medicines Agency (EMA) (Press release). 13 September 2019. Retrieved 19 September 2019.
20. 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.
21. 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.
22. 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.
23. 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.
24. Method Development and Validation for Quantification Of N, N-Dimethylformamide in Telmisartan Drugs Substance by Reverse Phase HPLC Using UV Detector. International Journal of All Research Education and Scientific Methods (IJARESM), ISSN: 2455-6211 Volume 10, Issue 7, July-2022.
25. Method Development and Validation for Quantification of Benzene and Ethylene Dichloride in Baclofen Drug Substance by GC-HS Using FID Detector. Indo American Journal of Pharmaceutical Sciences. 09 (7), 273-280, 2022.
26. Method Development and Validation for Quantification of Benzene and Mesityl Oxide in Rosuvastatin Calcium Drug Substance By GC-HS Using FID Detector. Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 10(1), 16-24, 2022.
27. Method Development and Validation of Five Nitrosamines Impurities Content in Telmisartan Drug Substance By GC-MS/MS. Indo American Journal of Pharmaceutical Sciences. 09 (7), 460-471, 2022.
28. Method Development and Validation of N-Nitrosodimethylamine (NDMA) Content in Metformin Hydrochloride Drug Substance By LC-MS/MS. International Journal of All Research Education and Scientific Methods (IJARESM), ISSN: 2455-6211 Volume 10, Issue 7, July-2022.