Skip to main content
SpringerLink
Log in

UV Spectroscopic Method for Determining pK a Values of Some Antipsychotic Drugs in Water and Acetonitrile–Water Binary Mixtures

  • Published:
Journal of Solution Chemistry Aims and scope Submit manuscript

Abstract

In this work, the dissociation constants of seven structurally related typical antipsychotic drugs, namely sertindole, olanzapine, fluphenazine, thioridazine, pimozide, mesoridazine and ziprasidone in water and 10, 20, 30 40 and 50 % (v/v) acetonitrile–water mixtures were determined at 298.15 K by UV/pH titration and correlated with the Kamlet and Taft solvatochromic parameters, π*, α and β. The electronic absorption spectra of these drugs were recorded at various pH values (pH = 2.0–12.0) at 210–350 nm. Calibration of the electrode system was done potentiometrically by Gran’s method. Data were processed using the program STAR (stability constants by absorbance readings). The results are in good concordance with literature values.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Taylor, P.J.: Hydrophobic properties of drugs. In: Hansch, C., Sammes, P.G., Taylor, J.B. (eds.) Comprehensive Medicinal Chemistry, vol. IV, pp. 241–294. Pregamon Press, Oxford (1990)

    Google Scholar 

  2. Oumada, F.Z., Ràfols, C., Rosés, M., Bosch, E.: Chromatographic determination of aqueous dissociation constants of some water-insoluble nonsteroidal antiinflammatory drugs. J. Pharm. Sci. 91, 991–999 (2002)

    Article  CAS  Google Scholar 

  3. Mizutani, M.: Die dissoziation der schwachen electrolyse in wasserig–alkoholischen losungen. Physik. Chem. 116, 350–358 (1925)

    CAS  Google Scholar 

  4. Takacs-Novak, K., Box, K.J., Avdeef, A.: Potentiometric pK a determination of water-insoluble compounds: validation study in methanol–water mixtures. Int. J. Pharm. 151, 235–238 (1997)

    Article  CAS  Google Scholar 

  5. Marcus, Y.: Preferential solvation. Part 3. Binary solvent mixtures. J. Chem. Soc. Faraday Trans. 85, 381–388 (1989)

    Article  CAS  Google Scholar 

  6. Roses, M., Rafols, C., Ortega, J., Bosch, E.: Solute–solvent and solvent–solvent interactions in binary solvent mixtures. Part 1. A comparison of several preferential solvation models for describing E T (30) polarity of bipolar hydrogen bond acceptor–cosolvent mixtures. J. Chem. Soc. Perkin Trans. 28, 1607–1615 (1995)

    Google Scholar 

  7. Şanlı, S., Altun, Y., Şanlı, N., Alsancak, G., Beltran, J.: Solvent effects on pK a values of some substituted sulfonamides in acetonitrile–water binary mixtures used in LC by the UV-spectroscopy. J. Chem. Eng. Data 54, 3014–3021 (2009)

    Article  Google Scholar 

  8. Şanlı, N., Şanlı, S., Alsancak, G.: Determination of dissociation constants of folinic acid (leucovorin), 5-fluorouracil and irinotecan in hydro–organic media by a spectrophotometric method. J. Chem. Eng. Data 55, 2695–2699 (2010)

    Article  Google Scholar 

  9. Şanlı, S., Şanlı, N., Alsancak, G.: Spectrophotmetric determination acidity constant of some macrolides in acetonitrile–water binary mixtures. Acta Chim. Slov. 57, 980–987 (2010)

    Google Scholar 

  10. Colak, N., Sanli, S., Sanli, N.: Spectrophotometric determination of acidity constants of some novel methotrexate-like compounds in water and acetonitrile–water binary mixtures. Rev. Anal. Chem. 29, 241–252 (2010)

    CAS  Google Scholar 

  11. Sanli, N., Sanli, S., Sızır, U., Gumustas, M., Ozkan, S.A.: Determination of pK a values of cefdinir and cefixime by LC and spectrophotometric methods and their analysis in pharmaceutical dosage forms. Chromatographia 73, 1171–1176 (2011)

    Article  CAS  Google Scholar 

  12. Hilal, S.H., El-Shabrawy, Y., Carreira, L.A., Karickhoff, S.W., Toubar, S.S., Rizk, M.: Estimation of the ionization pKa of pharmaceutical substances using the computer program sparc. Talanta 43, 607–619 (1996)

    Article  CAS  Google Scholar 

  13. Citores, M.J., Alonso, R.M., Fernandez, L.A.: Applications of computers in the study of solution equilibria V. APH, a program for the graphical evaluation of pK a values from spectrophotometric data. TrAC, Trends Anal. Chem. 11, 310–314 (1992)

    Article  CAS  Google Scholar 

  14. ACD lab ACD/Labs, Advanced Chemistry Development Inc., 90 Adelaide Street, West Toronto, Ontario, M5H3V9, Canada; http://www.acdlabs.com/ilab/. Accessed 3 March 2012

  15. http://www.chemaxon.com/marvin/sketch/index.jsp. Accessed 8 March 2012

  16. Glick, I.D., Murray, S.R., Vasudevan, P., Marder, S.R., Hu, R.J.: Treatment with atypical antipsychotics: new indications and new populations. J. Psychiatr. Res. 35, 187–191 (2001)

    Article  CAS  Google Scholar 

  17. Gran, G.: Determination of the equivalence point in potentiometric titrations. Part II. Analyst 7, 661–671 (1952)

    Article  Google Scholar 

  18. Gameiro, P., Reis, S., Lima, J.L.F.C., De Castro, B.: Calibration of pH glass electrodes by direct strong acid/strong base titrations under dilute conditions. Anal. Chim. Acta 405, 167–172 (2000)

    Article  CAS  Google Scholar 

  19. Beltran, J.L., Codony, R., Prat, M.D.: Evaluation of stability constants from multiwavelength absorbance data: program STAR. Anal. Chim. Acta 276, 441–454 (1993)

    Article  CAS  Google Scholar 

  20. SPARC V3.1. http://ibmlc2.chem.uga.edu/sparc/. Accessed 1 March 2012

  21. Altun, Y., Dogan-Topal, B., Uslu, B., Ozkan, S.A.: Anodic behavior of sertindole and its voltammetric determination in pharmaceuticals and human serum using glassy carbon and boron-doped diamond electrodes. Electrochim. Acta 54, 1893–1903 (2009)

    Article  CAS  Google Scholar 

  22. Balon, K., Riebeshl, R., Muller, B.: Drug liposome partitioning as a tool for the prediction of human passive intestinal absorption. Pharm. Res. 16, 882–888 (1999)

    Article  CAS  Google Scholar 

  23. Mohammadi, A., Amini, M., Hamedani, M.P., Torkabadi, H.H., Walker, R.B.: Study of the formation of artifacts following dichloromethane reaction with some nitrogenous drugs. Asian J. Chem. 20, 5573–5580 (2008)

    CAS  Google Scholar 

  24. Newton, D., Kluza, R.: pK values of medicinal compounds in pharmacy practice. Drug Intel. Clin. Phar. 12, 546–554 (1978)

    CAS  Google Scholar 

  25. Mannhold, R., Dross, K.P., Rekker, R.F.: Drug lipophilicity in QSAR practice: I. A comparison of experimental with calculative approaches. Quant. Struct. Act. Relat. 9, 21–28 (1990)

    Article  CAS  Google Scholar 

  26. El Tayar, N., Kilpatrick, G.J., Van De Waterbeemd, H., Testa, B., Jenner, P., Marsden, C.D.: Interaction of neuroleptic drugs with rat striatal D-a and D-2 dopamine receptors: a quantitative structure–affinity relationship study. Eur. J. Med. Chem. 23, 173–182 (1998)

    Article  Google Scholar 

  27. Basu, B., Garala, K., Thimmasetty, J.: Formulation and evaluation of pimozide buccal mucoadhesive patches. Int. J. Pharm. Sci. Nanotech. 2, 739–747 (2010)

    CAS  Google Scholar 

  28. Portell, A., Barbas, R., Font-Bardia, M., Dalmases, P., Prohens, R., Puigjaner, C.: New polymorphic hydrogen bonding donor-acceptor system with two temperature coincident solid–solid transitions. Cryst. Eng. Commun. 11, 91–795 (2009)

    Google Scholar 

  29. Merck Index: An encyclopedia of chemicals, drugs, and biologicals, 12th edn.,p. 7593. Merck Research Laboratory, Merck & Co. Inc., White House Station (1996)

  30. Barbosa, J., Berges, R., Sanz-Nebot, V., Toro, I.: Chromatographic behavior of ionizable compounds in liquid chromatography. Part 2. Standardization of potentiometric sensors and effect of pH and ionic strength on the retention of analytes using acetonitrile–water mobile phases. Anal. Chim. Acta 389, 43–52 (1999)

    Article  CAS  Google Scholar 

  31. González-Arjona, D., Mejias, J.A., Gonzalez, A.G.: Holmes: a program for target factor analysis. Anal. Chim. Acta 295, 119–125 (1994)

    Article  Google Scholar 

  32. Gonzáles-Arjona, D., Mejias, J.A., Gonzalez, A.G.: Corrigendum: Holmes: a program for target factor analysis. Anal. Chim. Acta 295, 119–125 (1994); by González-Arjona, D., Mejias, J.A., Gonzalez, A.G. Anal. Chim. Acta 297, 473 (1994)

Download references

Acknowledgments

The authors greatly acknowledge Dr. Jose L. Beltran from Universitat de Barcelona for kindly providing the spectral data processing software, STAR.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science and Arts, Usak University, Uşak, Turkey

    Senem Şanli

Authors
  1. Senem Şanli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Senem Şanli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Şanli, S. UV Spectroscopic Method for Determining pK a Values of Some Antipsychotic Drugs in Water and Acetonitrile–Water Binary Mixtures. J Solution Chem 42, 967–978 (2013). https://doi.org/10.1007/s10953-013-0006-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-013-0006-x

Keywords

Search

Navigation