Studies On New Methods For Determination Of Anticoagulant Warfarin Based On Fluorescence Effects Of CdTe Quantum Dots

Warfarin is an anticoagulant which belongs to the group of coumarins. It is usually applied and stored in the form of warfarin sodium. Warfarin is used clinically for the prevention and treatment of thromboembolic diseases. It is long-term or even lifetime used as an important oral anticoagulant for the patients after heart surgery. The development of the high-sensitivity method for determining warfarin is very important for the research of warfarin. In this thesis, the new high-sensitivity methods for the determination of warfarin were studied based on fluorescence effects of CdTe quantum dots,. The thesis includes the following:(1) A review of warfarin in terms of the anticoagulant mechanism, determination method and the research progress. The content and purposes of the thesis were proposed.(2) A method for determination of warfarin was developed, which based on fluorescence enhancement of warfarin with β-cyclodextrin. The methods have been successfully applied to determination of warfarin in tablets. Under the optimized conditions, the linear range and linear correlation coefficient (R2) was 0.05μmol·L-1～8μmol·L-1 and 0.9986, respectively. The detection limit(3σ/k) was 0.022μmol·L-1. This method is high-sensitivity and simple, which can be effectively used for determining anticoagulant warfarin.(3) Based on the fluorescence effect of CdTe quantum dots, a novel method for the determination of warfarin was developed in the paper. The CdTe quantum dots were synthesized. The mechanism of interaction between CdTe quantum dots and warfarin was investigated. The research results discovered for the first time that the fluorescence intensity of CdTe quantum dots could be enhanced with the increase of concentration of warfarin at low concentration(≤2μmol·L-1), and the fluorescence intensity of CdTe quantum dots would be weakened with the increase of concentration of warfarin at high concentration(≥2μmol·L-1). It shown that a double effect, the energy transfer and competition effects for the absorption of the excitation light, were existent for the interaction between warfarin and CdTe quantum dots.A new high-sensitivity method for determination of warfarin was proposed based on the effect of CdTe quantum dots. The method has been successfully applied to determination of warfarin in tablets. Under the optimized conditions, the linear ranges were 0.04 μmol·L-1～2 μmol·L-1 and 2μmol·L-1～100μmol·L-1. The linear correlation coefficients(R2) were 0.9957 and 0.9928, respectively. The detection limit(3σ/k) was 0.014 μmol·L-1. This new method for determining warfarin was high-sensitivity, fast, convenient, simple and practicable.(4) A novel method for the determination of warfarin was studied based on fluorescence effect of (mono-6-thio-β-CD)-CdTe quantum dots. (mono-6-thio-β-CD)-CdTe quantum dots were prepared. The mechanism of interaction between (mono-6-thio-β-CD)-CdTe quantum dots and warfarin was discussed. It shown that the fluorescence intensity of (mono-6-thio-β-CD)-CdTe quantum dots could be obviously enhanced in presence of warfarin with certain concentration. A new high-sensitivity method for the determination of warfarin was developed for the first time based on the fluorescence enhancement of (mono-6-thio-β-CD)-CdTe quantum dots. The proposed method has been successfully applied to determination of warfarin in tablets. Under optimized conditions, the linear range and linear correlation coefficient(R2) was 5.0×10-9mol·L-1～5.0×10-7mol·L-1 and 0.9977, respectively. The detection limit(3σ/k) was 3.2×10-9mol·L-1. This new method improved the sensitivity of determination for warfarin with the CdTe quantum dots system.(5) A method for the determination of warfarin was studied based on multilayer film of CdTe quantum dots. The multilayer films of CdTe QDs/PDDA were successfully prepared by electrostatic layer-by-layer self-assembly technology. The method was applied for rapid determination of warfarin. The results shown that the linear range, linear correlation coefficient(R2) and detection limit(3σ/k) was 0.1μmol·L-1～10μmol·L-1,0.9886 and 0.082μmol·L-1, respectively. This multilayer film of determination warfarin is good stability, easy to store and convenient. It provided a simple and practicable assay sensor for determination of warfarin.