Synthesis and Quantitation of Genotoxic impurity 5-cyano-2-((4-fluorophenyl) (hydroxy) benzyl 4-methyl benzene sulfonate in Escitalopram Oxalate by RP-UPLC

Authors

  • Krishna Katta
  • T. Siva Rao Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • T. Siva Rao Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • J. Mosesbabu Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • T. Siva Rao Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • J. Mosesbabu Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • D. Venugopala Rao Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • V. Malati Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • J. Mosesbabu Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • K. Sasikala Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • D. Venugopala Rao Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • D. Venugopala Rao Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • V. Malati Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • V. Malati Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • K. Sasikala Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003
  • K. Sasikala Department of Inorganic and analytical chemistry, Andhra University, Visakhapatnam, Hyderabad-530 003

DOI:

https://doi.org/10.7439/ijpc.v7i8.4292

Keywords:

Oral Lichen Planus, Genetics, pathogenesis

Abstract

The objective of the research work is to synthesize potential genotoxic impurity 5-cyano-2-((4-fluorophenyl) (hydroxyl) benzyl 4-methyl benzene sulfonate and to develop suitable UPLC method to quantify the above genotoxicimpurity in Escitalopram Oxalate at 15 ppm level. The above genotoxic impurity was synthesized by regio selective tosyaltion of Diol compound, under controlled temperature conditions at 0-5C with TsCl/pyridine/chloroform and characterized. A new UPLC method was developed by using UPLC BEH Shield RP18 100 x 2.1 mm, 1.7 column. The mobile phase used is the mixture of 0.05% ortho phosphoric acid and acetonitrile in the ratio of 8:2 (v/v) as solvent-A and 3:7 (v/v) as solvent-B at a flow rate of 0.4 mL/minute. Detector wavelength monitored at 228nm and column temperature was maintained at 27C. The UPLC method was validated as per International conference on harmonization guidelines. This method is proven as highly sensitive with a detection limit of 5ppm and quantification limit of 15 ppm. Regression analysis showed that the correlation coefficient value of 0.99999. The accuracy of the method was established based on the recovery obtained for 5-cyano-2-((4-fluorophenyl) (hydroxyl) benzyl 4-methyl benzene sulfonate. The present research work provided the route of synthesis as well as an advanced analytical methodology to quantify the above critical Genotoxic impurity known as 5-cyano-2-((4-fluorophenyl) (hydroxyl) benzyl 4-methyl benzene sulfonate in Escitalopram oxalate.

Downloads

Author Biography

  • Krishna Katta

    Analytical Research & development

    Manager

References

. Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended approaches (2008) US Department of Health and Human Services, Food and Drug administration, Centre for Drug Evaluation and Research CDER USA.

. Liu DQ, Sun M, Kord AS. Recent advances in trace analysis of pharmaceutical genotoxic impurities. J Pharm Biomed Anal 2010; 51: 999-1014.

. Yuabova, Holschlag ZY, Rodriguez DR, Qin SA, Papov C, et al. Genotoxic Impurities: A quantitative Approach. J Liq Chromatogr Relat Technol 2008; 31: 2318-2330.

. Guideline on Impurities in New Drug Substances, Q3A (R2), ICH.

. Muller L, Mauthe RJ, Riley CM, Andino MM, Antonis DD, et al. A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regul Toxicol Pharmacol 2006; 44: 198-211.

. IARC Monographs Program on the Evaluation of Carcinogenic Risks to Humans for ethyl methane-sulphonate 7 (1974) 245.

. Dobo KL, Greene N, Cyr MO, Caron S, Ku WW. The application of structure-based assessment to support safety and chemistry diligence to manage genotoxic impurities in active pharmaceutical ingredients during drug development. Regul Toxicol Pharmacol 2006; 44: 282-293.

. Kim C, Keum JE, Yu SH, Ko SY. Regioselective Mitsunobu-tosylation of 1, 2-diols. Bulletin of the Korean Chemical Society. 2009 Jul 20; 30(7):1671-4.

. Jouyban A, Parsa H. Genotoxic impurities in pharmaceuticals. InToxicity and Drug Testing 2012.

. ICH M7, Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, Current Step 4 version dated 23 June 2014.

. Edward JD. An impact analysis of the application of the threshold of toxicological concern concept to pharmaceuticals. J. Regul. Toxicol. Pharmacol, 2007; 49: 107-124.

. Kochi JK, Hammond GS. Benzyl tosylates. I. Preparation and properties. Journal of the American Chemical Society. 1953 Jul; 75(14):3443-4.

. Ding R, He Y, Wang X, Xu J, Chen Y, Feng M, Qi C. Treatment of alcohols with tosyl chloride does not always lead to the formation of tosylates. Molecules. 2011 Jul 1; 16(7):5665-73.

. Lohr LL, Jensen AJ, Sharp TR. NMR characterization of impurities. Separation Science and Technology. 2004 Dec 31; 5:301-39.

. Naga Malleswararao CS, Suryanaryana MV, Krishna K, Mukkanti K. Stability indicating uplc method for the rapid separation of related components of gemcitibine hydrochloride. Journal of Liquid Chromatography & Related Technologies. 2012 Jan 1; 35(18):2511-23.

. ICH, Q3A (R2) Guideline on Impurities in New Drug Substances, 2006. IFPMA, Geneva

Downloads

Published

2017-08-29

Issue

Vol. 7 No. 8 (2017): Aug

Section

Research Articles

License

Authors who publish with this journal agree to the following terms:

  • Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
  • Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
  • Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeThe Effect of Open Access).
  • The author must submit Copyright form After acceptance of the article.

How to Cite

1.
Synthesis and Quantitation of Genotoxic impurity 5-cyano-2-((4-fluorophenyl) (hydroxy) benzyl 4-methyl benzene sulfonate in Escitalopram Oxalate by RP-UPLC. Int J of Pharm Chem [Internet]. 2017 Aug. 29 [cited 2025 Jun. 6];7(8):131-8. Available from: https://ssjournals.co.in/index.php/ijpc/article/view/4292
Crossref
Scopus
Google Scholar
Europe PMC