Study On Rapid Fluorescence Detection Of Sunitinib And Dasatinib

Small molecule tyrosine kinase inhibitors(TKIs)with simple molecular structure,good targeting ability and few side effects were a kind of anticancer drug approved by FDA in 2001.TKIs were widely used in clinical practice,so there were high requirements for product synthesis,quality control and clinical monitoring.Thus,it is important to develop the fast detection method for TKIs.Fluorescence detection method,due to its advantages of low cost,simple operation,high sensitivity,strong practicability and good selectivity,demonstrated its special superiority for fast detection.Fluorescent nanomaterials,such as quantum dots(QDs)and carbon dots(CDs),etc.,had attracted much attention in recent years,and they were widely used as fluorescence probe in the fields of physics,chemistry,biology and medicine.In this thesis,the fast detection method for small TKIs was developed based on the novel fluorescence nanoprobe,enhancing its own fluorescence and the construction of colorimetric system.The specific contents are as follows:1.In this capture,citric acid and urea were used as carbon sources and nitrogen source to produce carbon dots(named as N-CDs)efficiently by solid-phase microwave method in only 3 min.Owing to the doping of N,N-CDs possessed high fluorescence quantum yield up to 15.9%.The fluorescence of N-CDs was stable to the environmental pH,ionic strength and ultraviolet radiation,and had good dispersiblity in water and water-soluble organic solvents with similar fluorescence properties.N-CDs had stronger fluorescence strength in organic solvents than in water,and ware quenched by sunitinib via the inner-filter effect.Therefore,N-CDs was used as a fluorescent probe for sunitinib detection.To eliminate the sample matrix effect and enhance the detection sensitivity,salting-out liquid-liquid extraction was employed.Combining the saltingout liquid-liquid extraction and the N-CDs probe,for the sunitinib in rat plasma,a good linear relationship in the range of 0.1 μg/m L to 7 μg/m L with good accuracy and recovery.LOQ was 100 ng/m L and LOD was 30 ng/m L.2.In this chapter,by controlling the environmental pH,the conjugate structure of dasatinib changed under alkaline conditions,so as to exponentially enhance its selffluorescence.Thus,via adjusting the alkaline condition,the sensitive detection of dasatinib could be conveniently and efficiently realized with good selectivity and specificity.It could directly detect dasatinib without any pretreatment.For dasatinib spiked rat plasma,good linearity in the range of 5-1000 ng/m L was obtained,with LOQ of 1 ng/m L and LOD of 0.3 ng/m L.Furthermore,a fluorescence colorimetric system was constructed by using Cd Te quantum dots(Cd Te QDS)as the red fluorescence reference,and the blue fluorescence of dasatinib as the responding signal.Further comibined with a mobile app,the method could be used for fast on-site detection.The linear range of colorimetric detection was 50-1500 ng/m L,which fully covered the effective plasma concentration of dasatinib for patients,confirming the applicability of the developed method for clinical monitoring in the field.3.The detection methods for small TKIs were summarized and prospected.