Warfarin New Method For Determination Of Serum Albumin Interaction Studies

Warfarin, a coumarin derivative, is widely used as an oral anticoagulant drug in the treatment and prevention of thromboembolic disorders. In this dissertation, new methods for determination of warfarin were developed. The interactions between warfarin and serum albumin were studied. The effect and the action mechanisms of ciprofloxacin and ofloxacin for warfarin were also discussed. The dissertation includes five parts.Chapter 1 ReviewA review of warfarin in terms of the anticoagulant mechanism, effect factors and determination methods was given. The progress of the interaction between warfarin and serum albumin was also reviewed. The research contents of the dissertation were proposed.Chapter 2 Fluorescence enhancement of HP-β-CD on anticoagulant warfarin and its applicationThe enhancement effect of HP-β-CD on the fluorescence of anticoagulant warfarin was studied in this paper. The inclusion property of warfarin with HP-β-CD was discussed. The enhancement effect and inclusion property of warfarin withβ-CD and HP-β-CD were also compared in the experiment. It shown that the fluorescence enhancement effect of HP-β-CD was higher than that ofβ-CD. A new method for the determination of warfarin with HP-β-CD had been developed based on the enhancement effect of HP-β-CD. The fluorescence intensity was linearly related to warfarin concentration over the range of 10.3-2266μg·L-1, and the detection limit was 2.92μg·L-1. The method has been satisfactorily applied to the determination of warfarin in tablets.Chapter 3 Determination of warfarin by fluorescence spectrometryA new method for determination of warfarin, based on fluorescence quenching of Triton X-100 by warfarin, has been developed. It shown that the fluorescence of Triton X-100 was quenched by warfarin through a static quenching process. Under the optimized experiment conditions, the fluorescence quenching intensity was linearly related to warfarin concentration over the range of 4×10-7-4×10-6mol·L-1, and the detection limit was 1.3×10-8 mol·L-1. The method was simple, rapid and has been successfully applied to the determination of warfarin in tablets. Chapter 4 Study on the Interaction between Warfarin and Serum Albumin by SpectrometryThe interactions between warfarin and bovine and human serum albumin (BSA and HSA) were investigated by spectrometry. The quenching mechanism of fluorescence of BSA by warfarin was discussed. The binding constants and binding numbers of warfarin and BSA were determined at different temperatures, respectively. According to the thermodynamic parameters, the main sorts of binding force was obtained. The distance between warfarin and BSA or HSA was calculated based on the Forster's theory of non-radiation energy transfer. The effect of warfarin on the conformation of BSA or HSA was also investigated using synchronous fluorescence spectrometry.Chapter 5 Studies on the effects of ciprofloxacin and ofloxacin on the interaction between warfarin and BSA by fluorescence spectrometryThe interactions between ciprofloxacin, ofloxacin and bovine serum albumin(BSA)were investigated by fluorescence spectrometry. The effect of ciprofloxacin or ofloxacin on the interaction between warfarin and BSA was also studied. It shown that ciprofloxacin, ofloxacin and BSA formed the complex. In the present of ciprofloxacin or ofloxacin, the binding abilities between warfarin and BSA was enhanced. The mechanisms of ciprofloxacin and ofloxacin affecting warfarin's effect were discussed.