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Journal of Pharmaceutical Research

Article

Quantification and Validation of a HPLC-UV Method for Simultaneous Analysis of Nitrosoamine Impurities (NDMA, NDEA and NDIPA) in Losartan
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Journal of Pharmaceutical Research

DOI: 10.18579/jopcr/v20i4.MS21084

Year: 2021, Volume: 20, Issue: 4, Pages: 43-49

Original Article

Quantification and Validation of a HPLC-UV Method for Simultaneous Analysis of Nitrosoamine Impurities (NDMA, NDEA and NDIPA) in Losartan

Santosh Patil ​✉ 1, Rajeev Chadar 1, Ashok Prasad 2, Poonam Koppula 1, Santhosh Koppula ​✉ 3

1 IPCA Laboratories Ltd, Vadodara, Gujarat , 391445, India
2 Ind Swift Laboratories Ltd, Chandigarh, India
3 Department of Chemistry, School of Sciences, GSFC University, Vadodara, Gujarat, ­ 391750, India
 
 ✉ Corresponding authors: Santosh Patil [email protected]
Santhosh Koppula [email protected]
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Impurity profiling is an important aspect in drug therapy for its safety and efficacy. The study of impurities of sartans, the first line antihypertensive drugs, has become critical due to presence of cancer causing N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-nitrosodiisopropylamine (NDIPA) in them, resulting from production and degradation process. These impurities have led to worldwide recall of products. Hence, a simple and accurate method has been developed and validated for simultaneous detection of NDMA, NDEA and NDIPA in Losartan using High Performance Liquid Chromatography - Ultra violet (HPLC - UV) system. The impurities were analyzed on Inertsil ODS 3V (250mm × 4.6mm, 5.0µm) analytical column by using water:methanol (60:40) as the mobile phase at a flow rate of 1.0 mL/min, with a run time of 30 mins. The method was developed for the acceptance limit of 0.64 ppm for NDMA, 0.177 ppm for NDEA and NDIPA respectively. On comparison with existing approaches, the developed method is fast, ideal for routine screening and is suitable for both laboratory and industrial uses.

 

Keywords: Losartan, HPLC - UV, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodiisopropylamine

References

  1. Asif H, Azim MS, Mitra M, Bhasin PS. A Review of Pharmacological and Pharmaceutical Profile of Irbesartan. Pharmacophore. 2011;2(6):240–250.
  2. Tsvetkova D, Obreshkova D, Ivanova S, Yankov V, Atanasov P. Quality Control of Impurities and Comparison of Pharmacokinetic Parameters of Angiotensin Receptor Antagonists. Journal of Multidisciplinary Engineering Science Studies (JMESS). 2016;2(7):647–661.
  3. Muszalska I, Sobczak A, Dołhań A, Jelińska A. Analysis of Sartans: A Review. Journal of Pharmaceutical Sciences. 2014;103(1):2–28. Available from: https://dx.doi.org/10.1002/jps.23760
  4. Ryan MJ, Didion SP, Mathur S, Faraci FM, Sigmund CD. Angiotensin II–Induced Vascular Dysfunction Is Mediated by the AT1AReceptor in Mice. Hypertension. 2004;43(5):1074–1079. Available from: https://dx.doi.org/10.1161/01.hyp.0000123074.89717.3d
  5. Sharma AM, Janke J, Gorzelniak K, Engeli S, Luft FC. Angiotensin Blockade Prevents Type 2 Diabetes by Formation of Fat Cells. Hypertension. 2002;40(5):609–611. Available from: https://dx.doi.org/10.1161/01.hyp.0000036448.44066.53
  6. Deka S, Bhattacharjee A. Safety of a drug molecule: What we have learned from recall of valsartan. Int. J. Curr. Med. Pharm. Res. 2018;4:3884–3887.
  8. Snodin DJ, Elder DP. Short commentary on NDMA (N-nitrosodimethylamine) contamination of valsartan products. Regulatory Toxicology and Pharmacology. 2019;103:325–329. Available from: https://dx.doi.org/10.1016/j.yrtph.2019.01.007
  14. Parr MK, Joseph JF. NDMA impurity in valsartan and other pharmaceutical products: Analytical methods for the determination of N-nitrosamines. Journal of Pharmaceutical and Biomedical Analysis. 2019;164:536–549. Available from: https://dx.doi.org/10.1016/j.jpba.2018.11.010
  17. Empl MT, Kammeyer P, Ulrich R, Joseph JF, Parr MK, Willenberg I, et al. The influence of chronic l-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats. Archives of Toxicology. 2015;89(11):2079–2087. Available from: https://dx.doi.org/10.1007/s00204-014-1341-4
  18. Crews C. The determination of N-nitrosamines in food. Quality Assurance and Safety of Crops & Foods. 2010;2(1):2–12. Available from: https://dx.doi.org/10.1111/j.1757-837x.2010.00049.x
  19. Seyler TH, Kim JG, Hodgson JA, Cowan EA, Blount BC, Wang L. Quantitation of Urinary Volatile Nitrosamines from Exposure to Tobacco Smoke*. Journal of Analytical Toxicology. 2013;37(4):195–202. Available from: https://dx.doi.org/10.1093/jat/bkt020
  20. Jurado-Sánchez B, Ballesteros E, Gallego M. Screening of N-nitrosamines in tap and swimming pool waters using fast gas chromatography. Journal of Separation Science. 2010;33(4-5):610–616. Available from: https://dx.doi.org/10.1002/jssc.200900679
  21. Li W, Chen N, Zhao Y, Guo W, Muhammd N, Zhu Y, et al. Online coupling of tandem liquid-phase extraction with HPLC-UV for the determination of trace N-nitrosamines in food products. Analytical Methods. 2018;10(15):1733–1739. Available from: https://dx.doi.org/10.1039/c8ay00014j
  22. Al-Kaseem M, Al-Assaf Z, Karabeet F. A Rapid, Validated RP-HPLC Method for the Determination of Seven Volatile N-Nitrosamines in Meat. Pharmacology & Pharmacy. 2014;05(03):298–308. Available from: https://dx.doi.org/10.4236/pp.2014.53037
  23. Zhang R, Hess DT, Qian Z, Hausladen A, Fonseca F, Chaube R, et al. Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia. Proceedings of the National Academy of Sciences. 2015;112(20):6425–6430. doi: 10.1073/pnas.1502285112
  24. Kodamatani H, Yamasaki H, Sakaguchi T, Itoh S, Iwaya Y, Saga M, et al. Rapid method for monitoring N -nitrosodimethylamine in drinking water at the ng/L level without pre-concentration using high-performance liquid chromatography-chemiluminescence detection. Journal of Chromatography A. 2016;1460:202–206. doi: 10.1016/j.chroma.2016.07.014
  25. Li X, He X, Dong Y, Jia L, He Q. Analysis of N -nitrosodiethylamine by ion chromatography coupled with UV photolysis pretreatment. Journal of Food and Drug Analysis. 2016;24(2):311–315. doi: 10.1016/j.jfda.2015.10.006

Copyright

© 2021 Published by Krupanidhi Educational Trust. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)

  • 16 February 2022

Year: 2021, Volume: 20, Issue: 4


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