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Year 2022, Volume: 26 Issue: 6, 1685 - 1693, 28.06.2025

Krishna Manjari Pawar Amgoth Sambasiva Rao Tummala

https://doi.org/10.29228/jrp.259
Cited By: 2

Abstract

References

  • [1] Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, Lu Y, Mansbach RS, Mather RJ, Rovetti CC, Sands SB, Schaeffer E, Schulz DW, Tingley FD, Williams KE. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacol. 2007;52:985-994. [CrossRef]
  • [2] Dani JA, De Biasi M. Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav. 2001;70(4):439-446. [CrossRef]
  • [3] Picciotto MR, Zoli M, Rimondini R, Léna C, Marubio LM, Pich EM, Fuxe K, Changeux JP. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature. 1998;391:173-177. [CrossRef]
  • [4] Tapper AR, McKinney SL, Nashmi R, Schwarz J, Deshpande P, Labarca C, Whiteaker P, Marks MJ, Collins AC, Lester HA. Nicotine activation of alpha4 receptors: sufficient for reward, tolerance, and sensitization. Science. 2004;306(5698):1029-1032. [CrossRef]
  • [5] Zieler-Brown L, Kyle J. Oral varenicline for smoking cessation. Ann Pharmacother. 2007;41(1):95-99. [CrossRef]
  • [6] Chantix: Package Insert. New York 2008. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021928s008lbl. (accessed on November 1, 2011).
  • [7] Benigni R, Bossa C. Structure alerts for carcinogenicity, and the Salmonella assay system: a novel insight through the chemical relational databases technology. Mutat Res Rev Mutat Res. 2008;659(3):248-261. [CrossRef]
  • [8] Ma L, Ma YN, Chen Z, Jiang Y. Structure alerts of genotoxic impurities. Chin J New Drugs. 2014;23:2106-2111.
  • [9] Liu DQ, Sun M, Kord AS. Recent advances in trace analysis of pharmaceutical genotoxic impurities. J Pharm Biomed Anal. 2010;51(5):999-1014. [CrossRef]
  • [10] Satheesh B, Kumarpulluru S, Raghavan V, Saravanan D. UPLC separation and quantification of related substances of varenicline tartrate tablet. Acta Chromatogr. 2010;22(2):207-218. [CrossRef]
  • [11] Kadi AA, Mohamed MS, Kassem MG, Darwish IA. A validated stability-indicating HPLC method for determination of varenicline in its bulk and tablets. Chem Cent J. 2011;5(1):30-35.
  • [12] Pietras R, Szymanska K, Kondej M, Gladysz A, Kowalczuk D. Development and validation of the HPLC method for varenicline determination in pharmaceutical preparation. Curr Issues Pharm Med Sci. 2017;30(3):142-146. [CrossRef]
  • [13] Balaji M, Rao AKMC, Ramakrishna K, Rao SV. Development and validation of related substances method for varenicline and its impurities. Pharm Lett. 2016;8(1):304-309.
  • [14] ICH Guideline. Q2 (R1): Validation of Analytical Procedure: Text and Methodology. ICH, London, 2005.

LC-MS/MS approach for the quantification of five genotoxic nitrosoimpurities in varenicline

Year 2022, Volume: 26 Issue: 6, 1685 - 1693, 28.06.2025

Krishna Manjari Pawar Amgoth Sambasiva Rao Tummala

https://doi.org/10.29228/jrp.259
Cited By: 2

Abstract

Using an LC-MS/MS (liquid chromatography-tandem mass spectrometry) method, four probable genotoxic impurities (PGIs) in the varenicline were quantified. With 0.7 mL/min of flow rate, the separation was performed using a Phenomenex kinetex F5 100 column (150 x 4.6 mm I.D., 2.6 μm) in gradient elution mode with formic acid of 0.1 percent in water as mobile phase A and formic acid of 0.1 percent in methanol as mobile phase B. MMR mode (Multiple reaction monitoring) is utilized to measure impurities with triple quadrupole mass detection using electrospray ionization. For all five PGIs, the approach was thoroughly verified as per ICH guidelines. In each case, this correlation coefficient was greater than 0.998. The recoveries for all chosen impurities were determined to be good, ranging between 83.7 to 107.3 percent. At a concentration level of 0.521-0.549 ppm, the proposed approach was sensitive enough to quantify all five PGIs. As a result, the proposed method for identifying and quantifying PGIs in varenicline is both practical and effective

Keywords

Varenicline genotoxic impurities liquid chromatography-tandem mass spectrometry sensitive

References

  • [1] Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, Lu Y, Mansbach RS, Mather RJ, Rovetti CC, Sands SB, Schaeffer E, Schulz DW, Tingley FD, Williams KE. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacol. 2007;52:985-994. [CrossRef]
  • [2] Dani JA, De Biasi M. Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav. 2001;70(4):439-446. [CrossRef]
  • [3] Picciotto MR, Zoli M, Rimondini R, Léna C, Marubio LM, Pich EM, Fuxe K, Changeux JP. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature. 1998;391:173-177. [CrossRef]
  • [4] Tapper AR, McKinney SL, Nashmi R, Schwarz J, Deshpande P, Labarca C, Whiteaker P, Marks MJ, Collins AC, Lester HA. Nicotine activation of alpha4 receptors: sufficient for reward, tolerance, and sensitization. Science. 2004;306(5698):1029-1032. [CrossRef]
  • [5] Zieler-Brown L, Kyle J. Oral varenicline for smoking cessation. Ann Pharmacother. 2007;41(1):95-99. [CrossRef]
  • [6] Chantix: Package Insert. New York 2008. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021928s008lbl. (accessed on November 1, 2011).
  • [7] Benigni R, Bossa C. Structure alerts for carcinogenicity, and the Salmonella assay system: a novel insight through the chemical relational databases technology. Mutat Res Rev Mutat Res. 2008;659(3):248-261. [CrossRef]
  • [8] Ma L, Ma YN, Chen Z, Jiang Y. Structure alerts of genotoxic impurities. Chin J New Drugs. 2014;23:2106-2111.
  • [9] Liu DQ, Sun M, Kord AS. Recent advances in trace analysis of pharmaceutical genotoxic impurities. J Pharm Biomed Anal. 2010;51(5):999-1014. [CrossRef]
  • [10] Satheesh B, Kumarpulluru S, Raghavan V, Saravanan D. UPLC separation and quantification of related substances of varenicline tartrate tablet. Acta Chromatogr. 2010;22(2):207-218. [CrossRef]
  • [11] Kadi AA, Mohamed MS, Kassem MG, Darwish IA. A validated stability-indicating HPLC method for determination of varenicline in its bulk and tablets. Chem Cent J. 2011;5(1):30-35.
  • [12] Pietras R, Szymanska K, Kondej M, Gladysz A, Kowalczuk D. Development and validation of the HPLC method for varenicline determination in pharmaceutical preparation. Curr Issues Pharm Med Sci. 2017;30(3):142-146. [CrossRef]
  • [13] Balaji M, Rao AKMC, Ramakrishna K, Rao SV. Development and validation of related substances method for varenicline and its impurities. Pharm Lett. 2016;8(1):304-309.
  • [14] ICH Guideline. Q2 (R1): Validation of Analytical Procedure: Text and Methodology. ICH, London, 2005.
There are 14 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Analytical Chemistry
Journal Section Articles
Authors

Krishna Manjari Pawar Amgoth

Sambasiva Rao Tummala

Publication Date June 28, 2025
Published in Issue Year 2022 Volume: 26 Issue: 6

Cite

APA Amgoth, K. M. P., & Tummala, S. R. (2025). LC-MS/MS approach for the quantification of five genotoxic nitrosoimpurities in varenicline. Journal of Research in Pharmacy, 26(6), 1685-1693. https://doi.org/10.29228/jrp.259
AMA Amgoth KMP, Tummala SR. LC-MS/MS approach for the quantification of five genotoxic nitrosoimpurities in varenicline. J. Res. Pharm. June 2025;26(6):1685-1693. doi:10.29228/jrp.259
Chicago Amgoth, Krishna Manjari Pawar, and Sambasiva Rao Tummala. “LC-MS/MS Approach for the Quantification of Five Genotoxic Nitrosoimpurities in Varenicline”. Journal of Research in Pharmacy 26, no. 6 (June 2025): 1685-93. https://doi.org/10.29228/jrp.259.
EndNote Amgoth KMP, Tummala SR (June 1, 2025) LC-MS/MS approach for the quantification of five genotoxic nitrosoimpurities in varenicline. Journal of Research in Pharmacy 26 6 1685–1693.
IEEE K. M. P. Amgoth and S. R. Tummala, “LC-MS/MS approach for the quantification of five genotoxic nitrosoimpurities in varenicline”, J. Res. Pharm., vol. 26, no. 6, pp. 1685–1693, 2025, doi: 10.29228/jrp.259.
ISNAD Amgoth, Krishna Manjari Pawar - Tummala, Sambasiva Rao. “LC-MS/MS Approach for the Quantification of Five Genotoxic Nitrosoimpurities in Varenicline”. Journal of Research in Pharmacy 26/6 (June 2025), 1685-1693. https://doi.org/10.29228/jrp.259.
JAMA Amgoth KMP, Tummala SR. LC-MS/MS approach for the quantification of five genotoxic nitrosoimpurities in varenicline. J. Res. Pharm. 2025;26:1685–1693.
MLA Amgoth, Krishna Manjari Pawar and Sambasiva Rao Tummala. “LC-MS/MS Approach for the Quantification of Five Genotoxic Nitrosoimpurities in Varenicline”. Journal of Research in Pharmacy, vol. 26, no. 6, 2025, pp. 1685-93, doi:10.29228/jrp.259.
Vancouver Amgoth KMP, Tummala SR. LC-MS/MS approach for the quantification of five genotoxic nitrosoimpurities in varenicline. J. Res. Pharm. 2025;26(6):1685-93.

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