Characterization of Interactions Between Fluoroquinolones and Human Serum Albumin by CE–Frontal Analysis
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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.
KeywordsCapillary electrophoresis Frontal analysis Thermodynamics Fluoroquinolones–human serum albumin interaction
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).
- 4.McMenany RH, Oncley JL (1958) J Biol Chem 233:1436–1447Google Scholar
- 5.Wainer IW (1993) Drugs stereochemistry: analytical methods and pharmacology, 2nd edn. Marcel Dekker, New YorkGoogle Scholar
- 8.Nicolle LE (1997) Management of acute uncomplicated pyelonephritis. In: Bergan T (Ed) Urinary tract infections, infectiology. Karger, Basel, p 8Google Scholar
- 20.Singh SS, Mehta J (2006) J Chromatogr B Anal Technol Biomed Life Sci 834:108–116Google Scholar
- 22.Yan C, Tong J, Xiong D, Liu Y, Pan Z (2006) Chin. J Anal Chem 34:796–800Google Scholar
- 36.Østergaard J, Schou C, Larsen C, Heegaard NHH (2002) Electrophoresis 23:2842–2853. doi: 10.1002/1522-2683(200209)23:17<2842::AID-ELPS2842>3.0.CO;2-B CrossRefGoogle Scholar
- 40.Wise R, Andrews JM, Ashby JP, Matthews RS (1988) Antimicrob Agents Chemother 32:617–622Google Scholar