Skip to main content
SpringerLink
Log in

Potential of High-Performance Liquid Chromatography for Distribution Coefficient Determination of 3-Hydroxyquinolin-4(1H)-one Derivatives

  • Original
  • Published:
Chromatographia Aims and scope Submit manuscript

Abstract

The potential of reversed-phase HPLC for the determination of distribution coefficient D 7.4 of selected 3-hydroxyquinolin-4(1H)-ones (3HQs) as compounds with significant biological activity was studied. Various stationary phases with C18 as well as hexyl-phenyl modification reflect current trends in RP-HPLC development such as higher sorbent silanophilicity, core–shell technology, hybrid and/or charged surface particles. Because of significant peak tailing of 3HQs at physiological pH on reversed-phase sorbents the separations at pH 3 were performed as well. Surprisingly, the pH change did not affect significantly the partition coefficients of 3HQs. Very affordable and common standards such as anisole, acetophenone, benzyl alcohol, brombenzene, ethylbenzoate and trichlorethylene were applied in the described methodology. The best linearity (R 2 0.9895) of the correlation between log P and log k w for standards was obtained for hexyl-phenyl sorbent, but this stationary phase was shown to be unsuitable for HPLC separation of 3HQs. The highest linearity (R 2 0.9499) of the relationship between log D 7.4 determined by the classic shake-flask method and log D determined by means of HPLC for 3HQs was attained with Cortecs C18+ column at pH 7.4. The described methodology with Cortecs C18+ as stationary phase offers fast and accurate estimation of log D 7.4 of the tested 3HQs. In an effort to increase the throughput of the HPLC method for log D 7.4 determination, we evaluated almost aqueous mobile phase that contained only 3 % of acetonitrile. Although a worse correlation between log D 7.4 determined by shake-flask method and HPLC with almost aqueous mobile phase was observed, the described procedure offers a very simple and high-throughput alternative for the estimation of log D 7.4.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Hradil P, Hlaváč J, Soural M, Hajdúch M, Kolář M, Večeřová R (2009) 3-Hydroxy-2-phenyl-4(1H)-quinolinones as promising biologically active compounds. Mini Rev Med Chem 9:696–702

    Article  CAS  Google Scholar 

  2. Motyka K, Hlaváč J, Soural M, Funk P (2010) Fluorescence properties of 2-aryl-3-hydroxyquinolin-4(1H)-one-carboxamides. Tetrahedron Lett 51:5060–5063

    Article  CAS  Google Scholar 

  3. Motyka K, Hlaváč J, Soural M, Hradil P, Krejčí P, Kvapil L, Weiss M (2011) Fluorescence properties of some 2-(4-aminosubstituted-3-nitrophenyl)-3-hydroxyquinolin-4(1H)-ones. Tetrahedron Lett 52:715–717

    Article  CAS  Google Scholar 

  4. Motyka K, Vaňková B, Hlaváč J, Soural M, Funk P (2011) Purine scaffold effect on fluorescence properties of purine-hydroxyquinolinone bisheterocycles. J Fluoresc 21:2207–2212

    Article  CAS  Google Scholar 

  5. Kadric J, Motyka K, Džubák P, Hajdúch M, Soural M (2014) Synthesis, cytotoxic activity and fluorescence properties of a set of novel 3-hydroxyquinolin-4(1H)-ones. Tetrahedron Lett 55:3592–3595

    Article  CAS  Google Scholar 

  6. Ortori CA, Dubern JF, Chhabra SF, Cámara M, Hardie K, Williams P, Barrett DA (2011) Simultaneous quantitative profiling of N-acyl-l-homoserine lactone and 2-alkyl-4(1H)-quinolone families of quorum-sensing signaling molecules using LC–MS/MS. Anal Bioanal Chem 399:839–850

    Article  CAS  Google Scholar 

  7. Lépine F, Milot S, Déziel E, He J, Rahme LG (2004) Electrospray/mass spectrometric identification and analysis of 4-hydroxy-2-alkylquinolines (HAQs) produced by Pseudomonas aeruginosa. J Am Soc Mass Spectrom 15:862–869

    Article  Google Scholar 

  8. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23:3–25

    Article  CAS  Google Scholar 

  9. Testa B, Crivori P, Reist M, Carrupt PA (2000) The influence of lipophilicity on the pharmacokinetic behavior of drugs: concepts and examples. Perspect Drug Discov 17:179–211

    Article  Google Scholar 

  10. Smith DA, Jones B, Walker DK (1996) Design of drugs involving the concepts and theories of drug metabolism and pharmacokinetics. Med Res Rev 16:243–266

    Article  CAS  Google Scholar 

  11. Braumann T (1986) Determination of hydrophobic parameters by reversed-phase liquid-chromatography—theory, experimental-techniques, and application in studies on quantitative structure–activity-relationships. J Chromatogr 373:191–225

    Article  CAS  Google Scholar 

  12. Giaginis C, Tsantili-Kakoulidou A (2008) Current state of the art in HPLC methodology for lipophilicity assessment of basic drugs. A review. J Liq Chromatogr Relat Technol 31:79–96

    Article  CAS  Google Scholar 

  13. El Tayar N, Tsantili-Kakoulidou A, Roethlisberger T, Testa B, Gal J (1988) Different partitioning behavior of sulfonyl-containing compounds in reversed-phase high-performance liquid chromatography and octanol-water systems. J Chromatogr 439:237–244

    Article  Google Scholar 

  14. Kaliszan R (1990) High-performance liquid-chromatographic methods and procedures of hydrophobicity determination. Quant Struct Act Relat 9:83–87

    Article  CAS  Google Scholar 

  15. Minick DJ, Frenz JH, Patrick MA, Brent DA (1988) A comprehensive method for determining hydrophobicity constants by reversed-phase high-performance liquid-chromatography. J Med Chem 31:1923–1933

    Article  CAS  Google Scholar 

  16. Bechalany A, Tsantili-Kakoulidou A, El Tayar N, Testa B (1991) Measurement of lipophilicity indexes by reversed-phase high-performance liquid-chromatography—comparison of 2 stationary phases and various eluents. J Chromatogr 541:221–229

    Article  CAS  Google Scholar 

  17. Neue UD, Tran K, Iraneta PC, Alden PA (2003) Characterization of HPLC packings. J Sep Sci 26:174–186

    Article  CAS  Google Scholar 

  18. Vervoor RJ, Debets AJ, Claessens HA, Hramers CA, de Jong GJ (2000) Optimisation and characterisation of silica-based reversed-phase liquid chromatographic systems for the analysis of basic pharmaceuticals. J Chromatogr A 897:1–22

    Article  CAS  Google Scholar 

  19. Lombardo F, Shalaeva MY, Tupper KA, Gao F (2001) ElogD(oct): a tool for lipophilicity determination in drug discovery. 2. Basic and neutral compounds. J Med Chem 44:2490–2497

    Article  CAS  Google Scholar 

  20. Liu X, Tanaka H, Yamauchi A, Testa B, Chuman H (2005) Determination of lipophilicity by reversed-phase high-performance liquid chromatography—influence of 1-octanol in the mobile phase. J Chromatogr A 1091:51–59

    Article  CAS  Google Scholar 

  21. Donavan SF, Pescatore MC (2002) Method for measuring the logarithm of the octanol-water partition coefficient by using short octadecyl-poly(vinyl alcohol) high-performance liquid chromatography columns. J Chromatogr A 952:47–61

    Article  Google Scholar 

  22. Liu X, Tanaka H, Yamauchi A, Testa B, Chuman H (2004) Lipophilicity measurement by reversed-phase high-performance liquid chromatography (RP-HPLC): a comparison of two stationary phases based on retention mechanisms. Helv Chim Act 87:2866–2876

    Article  CAS  Google Scholar 

  23. Bard B, Carrupt P-A, Martel S (2012) Determination of alkane/water partition coefficients of polar compounds using hydrophilic interaction chromatography. J Chromatogr A 1260:164–168

    Article  CAS  Google Scholar 

  24. Pidgeon C, Ong S, Liu H, Qui X, Pidgeon M, Dantzig AH, Munroe J, Hornback WJ, Kasher JS, Glunz L, Szczerba T (1995) IAM chromatography—an in vitro screen for predicting drug membrane-permeability. J Med Chem 38:590–594

    Article  CAS  Google Scholar 

  25. Bocian S, Buszewski B (2015) Comparison of retention properties of stationary phases imitated cell membrane in RP HPLC. J Chromatogr B 990:198–202

    Article  CAS  Google Scholar 

  26. Hradil P, Krejčí P, Hlaváč J, Wiedermannová I, Lyčka A, Bertolasi V (2004) Synthesis, NMR spectra and X-ray data of chloro and dichloro derivatives of 3-hydroxy-2-phenylquinolin-4(1H)-ones and their cytostatic activity. J Heterocyclic Chem 41:375–379

    Article  CAS  Google Scholar 

  27. Hradil P, Jirman J (1995) Collect Czech Chem Commun 60:1357–1366

    Article  CAS  Google Scholar 

  28. Hradil P, Hlaváč J, Lemr K (1999) Preparation of 1,2-disubstituted-3-hydroxy-4(1H)-quinolinones and the influence of substitution on the course of cyclization. J Heterocyclic Chem 36:141–144

    Article  CAS  Google Scholar 

  29. Giaginis C, Theocharis S, Tsantili-Kakoulidou A (2006) Contribution to the standardization of the chromatographic conditions for the lipophilicity assessment of neutral and basic drugs. Anal Chim Acta 573–574:311–318

    Article  Google Scholar 

  30. Schoenmakers PJ, Billiet HAH, de Galan L (1979) Influence of organic modifiers on the retention behaviour in reversed-phase liquid chromatography and its consequences for gradient elution. J Chromatogr 185:179–195

    Article  CAS  Google Scholar 

  31. Horvath C, Melander Molnar I (1976) Solvophobic interactions in liquid chromatography with nonpolar stationary phases. J Chromatogr 125(1976):129–156

    Article  CAS  Google Scholar 

  32. Mackay D, Shiu W-Y, Ma K-C, Lee SC (2006) Handbook of physical–chemical properties and environmental fate for organic chemicals, 2nd edn. CRC Press, Boca Raton

    Google Scholar 

  33. Martinez CHR, Dardonville C (2013) Rapid determination of ionization constants (pK(a)) by UV spectroscopy using 96-well microtiter plates. ACS Med Chem Lett 4:142–145

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The infrastructural part of this project (Institute of Molecular and Translational Medicine) was supported by the National program of sustainability (LO1304).

Author information

Authors and Affiliations

  1. Department of Organic Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, Olomouc, 77146, Czech Republic

    Tereza Volná & Kamil Motyka

  2. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 1333/5, Olomouc, 77900, Czech Republic

    Jan Hlaváč

Authors
  1. Tereza Volná
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamil Motyka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Hlaváč
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kamil Motyka.

Ethics declarations

Conflict of interest

Author Tereza Volná declares that she has no conflict of interest. Author Kamil Motyka declares that he has no conflict of interest. Author Jan Hlaváč declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Volná, T., Motyka, K. & Hlaváč, J. Potential of High-Performance Liquid Chromatography for Distribution Coefficient Determination of 3-Hydroxyquinolin-4(1H)-one Derivatives. Chromatographia 79, 1153–1163 (2016). https://doi.org/10.1007/s10337-016-3129-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10337-016-3129-6

Keywords

Search

Navigation