Advertisement

Journal of Analytical Chemistry

, Volume 73, Issue 6, pp 560–569 | Cite as

Ultra HPLC Method for Fixed Dose Combination of Azilsartan Medoxomil and Chlorthalidone: Identification and in silico Toxicity Prediction of Degradation Products

  • Gananadhamu SamanthulaEmail author
  • Debasish Swain
  • Gayatri Sahu
  • Shweta Bhagat
  • P. V. Bharatam
Articles
  • 33 Downloads

Abstract

The fixed dose combination of azilsartan medoxomil potassium and chlorthalidone has been introduced for the effective treatment of hypertension. In the present work a rapid, simple and accurate stability indicating ultra HPLC assay method has been developed. The separation of azilsartan medoxomil, chlorthalidone and their degradation products were accomplished on an Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm) column using mobile phase combination of 0.02% trifluoroacetic acid in water and acetonitrile in gradient mode. The forced degradation products were identified using liquid chromatography‒electrospray ionisation-quadrupole time of flight-tandem mass spectrometry (LC‒ESIQTOF–MS/MS) and accurate mass experiments. The in silico toxicities of the degradation products for both the drugs were evaluated. The proposed method was validated as per the ICH Q2 (R1) guideline for selectivity, linearity, precision, accuracy and robustness.

Keywords

azilsartan medoxomil potassium chlorthalidone ultra HPLC LC−ESI-QTOF−MS/MS in silico toxicity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Baker, W.L. and White, W.B., Ann. Pharmacother., 2011, vol. 45, no. 12, p. 1506.CrossRefPubMedGoogle Scholar
  2. 2.
    Lam, S., Cardiol. Rev., 2011, vol. 19, no. 6, p. 300.CrossRefPubMedGoogle Scholar
  3. 3.
    Sica, D., White, W.B., Weber, M.A., Bakris, G.L., Perez, A., Cao, C., Handley, A., and Kupfer, S., J. Clin. Hypertens., 2011, vol. 13, no. 7, p. 467.CrossRefGoogle Scholar
  4. 4.
    Ernst, M.E., Carter, B.L., Goerdt, C.J., Steffensmeier, J.J., Phillips, B.B., Zimmerman, M.B., and Bergus, G.R., Hypertension, 2006, vol. 47, no. 3, p. 352.CrossRefPubMedGoogle Scholar
  5. 5.
    Cushman, W.C., Bakris, G.L., White, W.B., Weber, M.A., Sica, D., Roberts, A., Lloyd, E., and Kupfer, S., Hypertension, 2012, vol. 60, no. 2, p. 310.CrossRefPubMedGoogle Scholar
  6. 6.
    Reynolds, D.W., Facchine, K.L., Mullaney, J.F., Alsante, K.M., Hatajik, T.D., and Motto, M.G., Pharm. Technol., 2002, vol. 26, p. 48.Google Scholar
  7. 7.
    Wegienka, L.C. and Weller, J.M., Arch. Int. Med., 1964, vol. 114, no. 2, p. 232.CrossRefGoogle Scholar
  8. 8.
    Blessy, M., Patel, R.D., Prajapati, P.N., and Agrawal, Y., J. Pharm. Anal., 2014, vol. 4, no. 3, p. 159.CrossRefPubMedGoogle Scholar
  9. 9.
    Sravani, P., Rubesh, S., Duganath, N., and Devanna, N., Int. J. Pharma Sci., 2014, vol. 4, no. 5, p. 725.Google Scholar
  10. 10.
    Swain, D., Patel, P.N., Palaniappan, I., Sahu, G., and Samanthula, G., Rapid Commun. Mass Spectrom., 2015, vol. 29, no. 15, p. 1437.CrossRefPubMedGoogle Scholar
  11. 11.
    Swain, D., Sahu, G., and Samanthula, G., J. Anal. Bioanal. Tech., 2015, vol. 6, no. 4, 254. doi 10.4172/2155-9872.1000254Google Scholar
  12. 12.
    Q1B Stability Testing: Photostability Testing of New Drug Substances and Products, Proc. Int. Conf. Harmonization, Geneva, 1996.Google Scholar
  13. 13.
    Q1A(R2) Stability Testing of New Drug Substances and Products, Proc. Int. Conf. Harmonization, Geneva, 2003.Google Scholar
  14. 14.
    Q2 (R1) Validation of Analytical Procedures, Proc. Int. Conf. Harmonization, Geneva, 2005.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • Gananadhamu Samanthula
    • 1
    Email author
  • Debasish Swain
    • 1
  • Gayatri Sahu
    • 2
  • Shweta Bhagat
    • 3
  • P. V. Bharatam
    • 3
  1. 1.National Institute of Pharmaceutical Education and Research (NIPER)Balanagar, Hyderabad, TelanganaIndia
  2. 2.United States Pharmacopeia (USP) India Pvt. Ltd.Hyderabad, TelanganaIndia
  3. 3.National Institute of Pharmaceutical Education and Research (NIPER)SAS Nagar, Mohali, PunjabIndia

Personalised recommendations