Chromatographia

, Volume 68, Issue 11–12, pp 969–975 | Cite as

Characterization of Interactions Between Fluoroquinolones and Human Serum Albumin by CE–Frontal Analysis

Original

Abstract

The binding of fluoroquinolones to the transport protein, human serum albumin (HSA), under simulated physiological conditions has been studied by capillary electrophoresis–frontal analysis (CE–FA). The binding of these drugs to human plasma was evaluated by using ultrafiltration and capillary electrophoresis. The free drug concentration [D]f at each HSA concentration was determined by the plateau height in the electropherograms and the calibration lines. The binding constants of fluoroquinolones and HSA were estimated using nonlinear regression with origin 7.5 software. The fluoroquinolones were found to show low affinity toward HSA, with binding constants ranging from 1.73 × 102 to 5.40 × 102 M−1. The percentages of protein binding (PB) for fluoroquinolones to HSA were between 8.6 and 22.2%, while the PB percentages for fluoroquinolones to human plasma were between 10.2 and 33.1%. It can be found that the PB percentages for fluoroquinolones to HSA are mostly lower than those for fluoroquinolones to human plasma. It suggests that HSA is the primary protein responsible for the binding of fluoroquinolones in human plasma. The thermodynamic parameters were obtained by CE–FA. The positive ∆H and ∆S values obtained by CE–FA showed that the binding reaction was an endothermic process, and the entropy drive the binding and hydrophobic interaction played major roles in the binding of fluoroquinolones to HSA.

Keywords

Capillary electrophoresis Frontal analysis Thermodynamics Fluoroquinolones–human serum albumin interaction 

Notes

Acknowledgments

This work was supported by the Specialized Research Funds of the Chinese Education Ministry and the Nature Science Funds of Hebei Province of China (B2008000583).

References

  1. 1.
    He XM, Carter DC (1992) Nature 358:209–215. doi: 10.1038/358209a0 CrossRefGoogle Scholar
  2. 2.
    Kandagal PB, Ashoka S, Seetharamappa J, Shaikh SMT (2006) J Pharm Biomed Anal 41:393–399. doi: 10.1016/j.jpba.2005.11.037 CrossRefGoogle Scholar
  3. 3.
    Liu JQ, Tian JN, Zhang JY, Hu ZD (2003) Anal Bioanal Chem 376:864–867. doi: 10.1007/s00216-003-1964-4 CrossRefGoogle Scholar
  4. 4.
    McMenany RH, Oncley JL (1958) J Biol Chem 233:1436–1447Google Scholar
  5. 5.
    Wainer IW (1993) Drugs stereochemistry: analytical methods and pharmacology, 2nd edn. Marcel Dekker, New YorkGoogle Scholar
  6. 6.
    Turnidge J (1999) Drugs 58:29–36. doi: 10.2165/00003495-199958002-00006 CrossRefGoogle Scholar
  7. 7.
    Albini A, Monti S (2003) Chem Soc Rev 32:238–250. doi: 10.1039/b209220b CrossRefGoogle Scholar
  8. 8.
    Nicolle LE (1997) Management of acute uncomplicated pyelonephritis. In: Bergan T (Ed) Urinary tract infections, infectiology. Karger, Basel, p 8Google Scholar
  9. 9.
    Kwong TC (1985) Clin Chim Acta 151:193–216. doi: 10.1016/0009-8981(85)90082-8 CrossRefGoogle Scholar
  10. 10.
    Hage DS, Noctor TAG, Wainer IW (1995) J Chromatogr A 693:23–32. doi: 10.1016/0021-9673(94)01009-4 CrossRefGoogle Scholar
  11. 11.
    Whitlam JB, Brown KF (1981) J Pharm Sci 70:146–150. doi: 10.1002/jps.2600700208 CrossRefGoogle Scholar
  12. 12.
    Ascoli G, Bertucci C, Salvadori P (1995) J Pharm Sci 84:737–741. doi: 10.1002/jps.2600840615 CrossRefGoogle Scholar
  13. 13.
    Fielding L (2003) Curr Top Med Chem 3:39–53. doi: 10.2174/1568026033392705 CrossRefGoogle Scholar
  14. 14.
    Chen H, Gong Z, Zhang Z (2006) J Pharm Biomed Anal 41:1412–1417. doi: 10.1016/j.jpba.2006.02.050 CrossRefGoogle Scholar
  15. 15.
    Parikh HH, McElwain K, Balasubramanian V, Leung W (2000) Pharm Res 17:632–637. doi: 10.1023/A:1007537520620 CrossRefGoogle Scholar
  16. 16.
    Martínez MA, Carril MM, Sagrado S, Villanueva RM (2007) J Chromatogr A 1147:261–269. doi: 10.1016/j.chroma.2007.02.054 CrossRefGoogle Scholar
  17. 17.
    Guo M, Lu WJ, Yi PG, Yu QS (2007) J Chem Thermodyn 39:337–343. doi: 10.1016/j.jct.2006.08.006 CrossRefGoogle Scholar
  18. 18.
    Zlotos G, Oehlmann M, Nickel P, Holzgrabe U (1998) J Pharm Biomed Anal 18:847–858. doi: 10.1016/S0731-7085(98)00220-9 CrossRefGoogle Scholar
  19. 19.
    Heinze A, Holzgrabe U (2006) Int J Pharm 311:108–112. doi: 10.1016/j.ijpharm.2005.12.022 CrossRefGoogle Scholar
  20. 20.
    Singh SS, Mehta J (2006) J Chromatogr B Anal Technol Biomed Life Sci 834:108–116Google Scholar
  21. 21.
    Barbato F, Martino G, Grumetto L, La Rotonda MI (2007) Eur J Pharm Sci 30:211–219. doi: 10.1016/j.ejps.2006.11.004 CrossRefGoogle Scholar
  22. 22.
    Yan C, Tong J, Xiong D, Liu Y, Pan Z (2006) Chin. J Anal Chem 34:796–800Google Scholar
  23. 23.
    Lu JQ, Jin F, Sun TQ, Zhou XW (2007) Int J Biol Macromol 40:299–304. doi: 10.1016/j.ijbiomac.2006.08.010 CrossRefGoogle Scholar
  24. 24.
    Tan F, Guo M, Yu QS (2005) Spectrochim Acta [A] 61:3006–3012. doi: 10.1016/j.saa.2004.11.019 CrossRefGoogle Scholar
  25. 25.
    Wang Y, Feng L, Jiang C (2005) Spectrochim Acta A 61:2909–2914. doi: 10.1016/j.saa.2004.11.004 CrossRefGoogle Scholar
  26. 26.
    Seetharamappa J, Kamat BP (2005) J Pharm Biomed Anal 39:1046–1050. doi: 10.1016/j.jpba.2005.05.013 CrossRefGoogle Scholar
  27. 27.
    Zacharis CK, Theodoridis GA, Podgornik A, Voulgaropoulos AN (2006) J Chromatogr A 1121:46–54. doi: 10.1016/j.chroma.2006.04.049 CrossRefGoogle Scholar
  28. 28.
    Rundlett KL, Armstrong DW (2001) Electrophoresis 22:1419–1427 10.1002/1522-2683(200105)22:7<1419::AID-ELPS1419>3.0.CO;2-VCrossRefGoogle Scholar
  29. 29.
    Oravcová J, Bőhs B, Lindner W (1996) J Chromatogr B Anal Technol Biomed Life Sci 677:1–28. doi: 10.1016/0378-4347(95)00425-4 CrossRefGoogle Scholar
  30. 30.
    Heegaard NHH, Kennedy RT (1999) Electrophoresis 20:3122–3133. doi:10.1002/(SICI)1522-2683(19991001)20:15/16<3122::AID-ELPS3122>3.0.CO;2-MCrossRefGoogle Scholar
  31. 31.
    Østergaard J, Heegaard NHH (2003) Electrophoresis 24:2903–2913. doi: 10.1002/elps.200305526 CrossRefGoogle Scholar
  32. 32.
    Liu SW, Zhang LW, Zhang XX (2006) Anal Sci 22:1515–1518. doi: 10.2116/analsci.22.1515 CrossRefGoogle Scholar
  33. 33.
    Zhang LW, Wang K, Zhang XX (2007) Anal Chim Acta 603:101–110. doi: 10.1016/j.aca.2007.09.021 CrossRefGoogle Scholar
  34. 34.
    Busch MHA, Carels LB, Boelens HFM, Kraak JC (1997) J Chromatogr A 777:311–328. doi: 10.1016/S0021-9673(97)00369-5 CrossRefGoogle Scholar
  35. 35.
    Jia Z, Ramstad T, Zhong M (2002) J Pharm Biomed Anal 30:405–413. doi: 10.1016/S0731-7085(02)00223-6 CrossRefGoogle Scholar
  36. 36.
    Østergaard J, Schou C, Larsen C, Heegaard NHH (2002) Electrophoresis 23:2842–2853. doi: 10.1002/1522-2683(200209)23:17&lt;2842::AID-ELPS2842&gt;3.0.CO;2-B CrossRefGoogle Scholar
  37. 37.
    Martínez-Pla JJ, Martínez-Gómez MA, Martín-Biosca Y, Sagrado S (2004) Electrophoresis 25:3176–3185. doi: 10.1002/elps.200406049 CrossRefGoogle Scholar
  38. 38.
    Kays MB, Conklin M (2000) Pharmacotherapy 20:1313–1317. doi: 10.1592/phco.20.17.1310.34899 CrossRefGoogle Scholar
  39. 39.
    Wise R, Andrews JM, Danks G (1984) J Antimicrob Chemother 13:237–244. doi: 10.1093/jac/13.3.237 CrossRefGoogle Scholar
  40. 40.
    Wise R, Andrews JM, Ashby JP, Matthews RS (1988) Antimicrob Agents Chemother 32:617–622Google Scholar
  41. 41.
    Fish DN, Chow AT (1997) Clin Pharmacokinet 32:101–119. doi: 10.2165/00003088-199732020-00002 CrossRefGoogle Scholar
  42. 42.
    Ross PD, Subramanian S (1981) Biochemistry 20:3096–3102. doi: 10.1021/bi00514a017 CrossRefGoogle Scholar

Copyright information

© Vieweg+Teubner | GWV Fachverlage GmbH 2008

Authors and Affiliations

  1. 1.College of Chemistry and Environmental Science, Key Laboratory of Analytical Science and Technology of Hebei ProvinceHebei UniversityBaodingChina

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