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Thermodynamic protonation constants of vardenafil by the nonlinear regression of multiwavelength pH-spectrophotometric titration data

  • Research Article
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Central European Journal of Chemistry

Abstract

pH-spectrophotometric titration data were used to determine protonation constants of vardenafil at different ionic strengths I and temperatures of 25°C and 37°C. The use of two different multiwavelength and the multivariate treatment of spectral data, SPECFIT32 and SQUAD(84) nonlinear regression analyses and INDICES factor analysis is presented. The reliability of the protonation constants of the drug was proven with goodness-of-fit tests of the pH-spectra. The thermodynamic protonation constants log K T i were estimated by a nonlinear regression of (log K, I) data using the Debye-Hückel equation, yielding log K T4 = 3.59(1) and 3.26(1), log K T3 = 5.64(1) and 5.81(1), log K T2 = 9.41(1) and 8.59(2), log K T1 = 10.92(2) and 10.05(1) at 25°C and 37°C, where the figure in brackets is the standard deviation in last significant digit. Concurrently, the experimental determination of four thermodynamic protonation constants was combined with the computational prediction of the MARVIN program based on knowledge of the chemical structures of the drug and was in good agreement with its experimental value. The factor analysis of spectra in the INDICES program predicts the correct number of light-absorbing components when the instrument error is known and when the signal-to-error ratio SER is higher than 10.

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References

  1. Z. Bartošová, D. Jirovský, A. Horna, J. Chrom. A 1218, 7996 (2011)

    Article  Google Scholar 

  2. G. M. Keating, L.J. Scott, Drugs 63, 2673 (2003)

    Article  CAS  Google Scholar 

  3. J. D. Corbin, A. Beasley, M.A. Blount, S.H. Francis, Neurochem. Int. 45, 859 (2004)

    Article  CAS  Google Scholar 

  4. T. Klotz, R. Sachse, A. Heidrich, F. Jockenhovel, G. Rohde, G. Wensing, R. Horstmann, R. Engelmann, World J. Urol. 19, 32 (2001)

    Article  CAS  Google Scholar 

  5. K. R. Schonnemann, M. Andersen, M. Yilmaz, H.A. Jensen, L.W. Vestermark, P. Pfeiffer, J. Clin. Oncol. 27, (2009)

  6. S. H. Hillal, S.W. Karickhoff, L.A. Carriera, in National Exposure Research Laboratory EPA/600/R-03/030 (Office of Research and Development, U.S. Enviromental protection Agency, NC 27711, USA, March 2003)

    Google Scholar 

  7. Z. Gulyás, G. Pöcze, A. Petz, F. Darvas, Pallas cluster—a new solution to accelerate the high-throughut ADME-TOX prediction, ComGenex-CompuDrug, PKALC/PALLAS 2.1 CompuDrug ChemistryLtd., 〈http://www.compudrug.com〉

  8. B. Sirohi, S. Sutherland, E. Killick, C. Mikropoulos, A. Constantinodou, S. Ashley, N. Shaunak, M. O’Brien, S. Johnston, I.E. Smith, Ann. Oncol. 19, 133 (2008)

    Article  Google Scholar 

  9. United States Pharmacopeial Convention USP DI.: Drug information for the health care provider (University of Chicago, USA, 1996) vol. 3, p. 664, ISBN 0740-4174

    Google Scholar 

  10. Y. Hotta, M. Hattori, T. Kataoka, R. Ohno, M. Mikumo, Y. Maeda, K. Kimura, J. Sex. Med. 8, 705 (2011)

    Article  CAS  Google Scholar 

  11. J. I. Martinez-Salamanca, J. Carballido, I. Eardley, F. Giuliano, C. Gratzke, R. Rosen, A. Salonia, C. Stief, Eur. Urol. 60, 527 (2011)

    Article  CAS  Google Scholar 

  12. Y. Ishibashi, T. Matsui, M. Takeuchi, S. Yamagishi, Clin. Exp. Med. 11, 131 (2011)

    Article  CAS  Google Scholar 

  13. M. Meloun, S. Bordovská, T. Syrový, A. Vrána, Anal. Chim. Acta 580, 107 (2006)

    Article  CAS  Google Scholar 

  14. M. Meloun, T. Syrový, S. Bordovská, A. Vrána, Anal. Bioanal. Chem. 387, 941 (2007)

    Article  CAS  Google Scholar 

  15. M. Meloun, M. Javůrek, J. Havel, Talanta 33, 513 (1986)

    Article  CAS  Google Scholar 

  16. D. J. Leggett, Computational methods for the determination of formation constants (Plenum Press, New York, 1985)

    Book  Google Scholar 

  17. H. Gampp, M. Maeder, C.J. Meyer, A.D. Zuberbuhler, Talanta 32, 95 (1985)

    Article  CAS  Google Scholar 

  18. H. Gampp, M. Maeder, C.J. Meyer, A.D. Zuberbuhler, Talanta 32, 257 (1985)

    Article  CAS  Google Scholar 

  19. H. Gampp, M. Maeder, C.J. Meyer, A.D. Zuberbuhler, Talanta 32, 1133 (1985)

    Article  CAS  Google Scholar 

  20. M. Meloun, Z. Ferenčíková, A. Vrána, J. Chem. Thermodyn 43, 930 (2011)

    Article  CAS  Google Scholar 

  21. S-Plus (MathSoft, Seattle, USA, 1999)

  22. M. Meloun, J. Čapek, P. Mikšík, R. G. Brereton, Analytica Chimica Acta 423, 51 (2000)

    Article  CAS  Google Scholar 

  23. M. Meloun, V. Říha, J. Žáček, Chem Listy 82, 765 (1988)

    CAS  Google Scholar 

  24. M. Meloun, J. Havel, E. Högfeldt, Computation of Solution Equilibria: A Guide to Methods in Potentiometry, Extraction, and Spectrophotometry (Prentice Hall, UK, 1988)

    Google Scholar 

  25. J. J. Kankare, Analytical Chemistry 42, 1322 (1970)

    Article  CAS  Google Scholar 

  26. M. Meloun, J. Militký, M. Forina, Chemometrics for analytical chemistry, Volume 1: PC-Aided Statistical Data Analysis (Ellis Horwood, Chichester, 1992)

    Google Scholar 

  27. SPECFIT/32 (Spectrum Software Associates, 197M Boston Post Road West, Marlborough, MA, 01752 U. SPECFIT/32 (Spectrum Software Associates, 197M Boston Post Road West, Marlborough, MA, 01752 U.S.A., 2004)

  28. Origin 8.0 (OriginLab Corporation, One Roundhouse Plaza, Suite 303, Northampton, MA 01060, USA.)

  29. ADSTAT (TriloByte Statistical Software Ltd., Pardubice, Czech Republic)

  30. M. Meloun, S. Bordovská, T. Syrový, J. Phys. Org. Chem. 43, 690 (2007)

    Article  Google Scholar 

  31. M. Meloun, D. Burkoňová, T. Syrový, A. Vrána, Anal. Chim. Acta 486, 125 (2003)

    Article  CAS  Google Scholar 

  32. M. Meloun, Z. Ferenčíková, H. Málková, T. Pekárek, Centr. Eur. J. Chem. 10, 338 (2012)

    Article  CAS  Google Scholar 

  33. M. Meloun, Z. Ferenčíková, A. Vrána, Am. J. Anal. Chem. 1, 14 (2010)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Analytical Chemistry, University of Pardubice, CZ 532 10, Pardubice, Czech Republic

    Milan Meloun, Zuzana Ferenčíková & Irena Niesnerová

  2. Zentiva k.s., CZ 102 37, Prague, Czech Republic

    Tomáš Pekárek

Authors
  1. Milan Meloun
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  2. Zuzana Ferenčíková
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  3. Irena Niesnerová
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  4. Tomáš Pekárek
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Correspondence to Milan Meloun.

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Meloun, M., Ferenčíková, Z., Niesnerová, I. et al. Thermodynamic protonation constants of vardenafil by the nonlinear regression of multiwavelength pH-spectrophotometric titration data. cent.eur.j.chem. 11, 271–279 (2013). https://doi.org/10.2478/s11532-012-0150-y

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