Journal of Analytical Chemistry

, Volume 72, Issue 5, pp 567–574 | Cite as

Reverse phase HPLC determination of sunitinib malate using UV detector, its isomerisation study, method development and validation

  • Mohsen Padervand
  • Solmaz Ghaffari
  • Hossein Attar
  • Mahdieh Mohammad Nejad


Sunitinib malate, as an anticancer compound and a multi-targeted tyrosine-kinase inhibitor for treatment of glioma, was comprehensively studied by using different liquid chromatography methods. Since sunitinib malate shows Z-E isomerism, various reverse phase high performance liquid chromatography (RP-HPLC) programs were designed to access quantitative determination and good separation of Z-E stereoisomers. Moreover, some impurities including N-oxide and impurity B were to be separated from the main isomer with acceptable resolution. In the present work, different RP-HPLC programs were developed in which the type of mobile phase, flow rate, pH, and temperature were optimized to reach the best analysis conditions and control the rate of Z to E conversion. In addition, the effect of some operational parameters during the solution preparation including initial concentration of the analyte, temperature, pH, and type of solvent on the stability of Z isomer were investigated. The opted conditions for quantitative analysis were C8-Hector column as stationary phase, methanol as solvent, ammonium acetate buffer containing triethylamine as mobile phase, the pH of mobile phase of 8.5, the flow rate of 1.0 mL/min, and detection at 425 nm. In this situation the peaks of E and Z isomers were at 16.3 and 19.7 min. Full validation of the designed method was done based on ICH guidelines.


sunitinib malate RP-HPLC method validation isomerism 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Atkins, M., Jones, C.A., and Kirkpatrick, P., Nat. Rev. Drug Discovery, 2006, vol. 5, p. 279.CrossRefGoogle Scholar
  2. 2.
    Faivre, S., Demetri, G., Sargent, W., and Raymond, E., Nat. Rev. Drug Discovery, 2007, vol. 6, p. 734.CrossRefGoogle Scholar
  3. 3.
    FDA Labeling information, 2009. Scholar
  4. 4.
    Rini, B.I., Expert Opin. Pharmacother., 2007, vol. 8, p. 2359.CrossRefGoogle Scholar
  5. 5.
    Goodman, V.L., Rock, E.P., Dagher, R., Ramchandani, R.P., Abraham, S., Gobburu, J.V.S., Booth, B.P., Verbois, S.L., Morse, D.E., Liang, C.Y., Chidambaram, N., Jiang, J.X., Tang, S., Mahjoob, K., Justice, R., and Pazdur, R., Clin. Cancer Res., 2007, vol. 13, p. 1367.CrossRefGoogle Scholar
  6. 6.
    Kulke, M.H., Lenz, H.J., Meropol, N.J., Posey, J., Ryan, D.P., Picus, J., Bergsland, E., Stuart, K., Tye, L., Huang, X., Li, J.Z., Baum, C.M., and Fuchs, C.S., J. Clin. Oncol., 2008, vol. 26, p. 3403.CrossRefGoogle Scholar
  7. 7.
    Demetri, G.D., Van-Oosterom, A.T., Garrett, C.R., Blackstein, M.E., Shah, M.H., Verweij, J., Mcarthur, G., Judson, I.R., Heinrich, M.C., Morgan, J.A., Desai, J., Fletcher, C.D., George, S., Bello, C.L., Huang, X., Baum, C.M., and Casali, P.G., Lancet, 2006, vol. 368, p. 1329.CrossRefGoogle Scholar
  8. 8.
    Socinski, M.A., Novello, S., Brahmer, J.R., Rosell, R., Sanchez, J.M., Belani, C.P., Govindan, R., Atkins, J.N., Gillenwater, H.H., Pallares, C., Tye, L., Selaru, P., Chao, R.C., and Scagliotti, G.V., J. Clin. Oncol., 2008, vol. 26, p. 650.CrossRefGoogle Scholar
  9. 9.
    Gale, N.W. and Yancopoulos, G.D., Genes Dev., 1999, vol. 13, p. 1055.CrossRefGoogle Scholar
  10. 10.
    Sistla, A. and Shenoy, N., Drug Dev. Ind. Pharm., 2005, vol. 31, p. 1001.CrossRefGoogle Scholar
  11. 11.
    Autrey, R.L. and Tahk, F.C., Tetrahedron, 1967, vol. 23, p. 901.CrossRefGoogle Scholar
  12. 12.
    Morales-Rios, M.S., Mora-Perez, Y., and Nathan, J.P., Magn. Reson. Chem., 1992, vol. 30, p. 1153.CrossRefGoogle Scholar
  13. 13.
    Benniston, A.C. and Harriman, A., J. Chem. Soc., Faraday Trans., 1994, vol. 90, p. 2627.CrossRefGoogle Scholar
  14. 14.
    Gotze, L., Hegele, A., Metzelder, S.K., Renz, H., and Nockher, W.A., Clin. Chim. Acta, 2012, vol. 413, p. 143.CrossRefGoogle Scholar
  15. 15.
    Haouala, A., Zanolari, B., Rochat, B., Montemurro, M., Zaman, K., Duchosal, M.A., Ris, H.B., Leyvraz, S., Widmer, N., and Decosterd, L.A., J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2009, vol. 877, p. 1982.CrossRefGoogle Scholar
  16. 16.
    Oberoi, R.K., Mittapalli, R.K., Fisher, J., and Elmquist, W.F., Chromatographia, 2013, vol. 1, p. 23.Google Scholar
  17. 17.
    Minkin, P., Zhao, M., Chen, Z., Ouwerkerk, J., Gelderblom, H., and Baker, S.D., J. Chromatogr. B: Anal. Technol. Biomed. Life Sci., 2008, vol. 874, p. 84.CrossRefGoogle Scholar
  18. 18.
    Qiu, F., Bian, W., Li, J., and Ge, Z., Biomed. Chromatogr., 2013, vol. 27, p. 615.CrossRefGoogle Scholar
  19. 19.
    Lankheet, N.A., Blank, C.U., Mallo, H., Adriaansz, S., Rosing, H., Schellens, J.H., Huitema, A.D., and Beijnen, J.H., J. Anal. Toxicol., 2011, vol. 35, p. 558.CrossRefGoogle Scholar
  20. 20.
    ICH Q2B: Validation of Analytical Procedures: Methodology, 1997, 1–8.Google Scholar
  21. 21.
    Riley, C.M., Thomas, W.R., and Shelley, R.R., Specification of Drug Substances and Products: Development and Validation of Analytical Methods, Maryville, MO Elsevier, 2013.Google Scholar
  22. 22.
    Maafi, M. and Brown, R.G., J. Photochem. Photobiol., A, 2007, vol. 187, p. 319.CrossRefGoogle Scholar
  23. 23.
    Maafi, M. and Maafi, W., Int. J. Pharm., 2014, vol. 471, p. 536.CrossRefGoogle Scholar
  24. 24.
    Mounir, M. and Lee, L.Y., J. Pharm. Biomed. Anal., 2015, vol. 110, p. 34.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • Mohsen Padervand
    • 1
    • 2
  • Solmaz Ghaffari
    • 1
    • 3
    • 4
    • 5
  • Hossein Attar
    • 1
    • 6
  • Mahdieh Mohammad Nejad
    • 3
  1. 1.Research and Development Department, Quality Control LaboratoryTofigh Daru Research and Engineering Co.TehranIran
  2. 2.Faculty of Science, Department of ChemistryUniversity of Maragheh, MaraghehTehranIran
  3. 3.Instrumental Analysis Department, Quality Control LaboratoryTofigh Daru Research and Engineering Co.TehranIran
  4. 4.Young Researchers and Elite Club, Pharmaceutical Sciences BranchIslamic Azad University (IAUPS)TehranIran
  5. 5.Pharmaceutical Sciences Research Center, Pharmaceutical Sciences BranchIslamic Azad University (IAUPS)TehranIran
  6. 6.Chemical Engineering Department, Engineering and Technology Faculty, Sciences and Research BranchIslamic Azad UniversityTehranIran

Personalised recommendations