Application Of Microfluidic Chip Electrophoresis With Contactless Conductivity Detection In Pharmaceutical Analysis

Microfluidic chip is micro-electrophoresis analysis device engraved in micro-channels,channel networks of glass,quartz,plastic,paper and other materials to perform tasks such as sample processing,transfer,separation and detection.Microfluidic chip has unique advantages such as fast analysis speed,high-efficiency separation performance,low reagent consumption and low cost.Microfluidic chip has been used in many fields and directions in recent years.Among them,pharmaceutical analysis is one of the most active research and application fields.At present,contactless conductivity detection is one of the most commonly used detection methods for microfluidic chip technology in pharmaceutical analysis.Because contactless conductivity detector has less disturbed relatively,and the universality of drug detection is good.Microfluidic chip with contactless conductivity detection has related application research in pharmaceutical preparation analysis,drug analysis in biological samples and other directions.Based on the previous research work of our research group,this thesis focuses on the "Application of Microfluidic Chip with Contactless Conductivity Detection in Pharmaceutical Analysis of Alzheimer’s Disease",and has carried out the following series of research work:New methods for the determination of memantine hydrochloride in memantine hydrochloride tablets,donepezil in donepezil hydrochloride tablets and galantamine in galantamine hydrobromide tablets were developed using microfluidic chip with contactless conductivity detection.Meanwhile,it had a development for the determination of insoluble drugs by microfluidic chip with contactless conductivity detection.Moreover,a method to improve the sensitivity of microfluidic chip with contactless conductivity detection was designed,which was applied to the detection of galantamine in human plasma.The theory and mechanism of this method were preliminarily discussed.It provided a new method for drug analysis in human plasma by microfluidic chip with contactless conductivity detection.The detection conditions of memantine hydrochloride are as follow:2%-3.0-2.0 mM dimethyl sulfoxide-triethylamine-phosphate buffer solution(pH 3.3);injection time:10 s;separation voltage:2.0 kV.The linear range is 10-2000 μg/mL,the detection limit(LOD)is 7 μg/mL.The recovery is between 94.4-100.1%,and the method has good precision,stability,repeatability and accuracy.The retention time of memantine hydrochloride is lower than 18 s.The detection conditions of donepezil are as follow:2%-15-5 mM dimethyl sulfoxide-triethylamine-phosphate buffer solution(pH 6.24);injection time:10 s;separation voltage:2.0 kV.The linear range is 70-2000 μg/mL,and the detection limit(LOD)is 19 μg/mL.The recovery was between96.2～103.9%.This method has good precision,repeatability and accuracy,and the retention time of donepezil is about 1.2 min.The detection conditions of galantamine hydrobromide are as follow:10-10 mM triethylamine-boric acid buffer solution(pH 10.17);injection time:10 s;separation voltage:2.0 kV.The linear range is 9-2000 μg/mL,and the detection limit(LOD)is 2 μg/mL,respectively.The recovery is between 95.8-104.9%.The method has good precision,stability,repeatability and accuracy.The retention time of galantamine is about 48 s.In addition,a method to improve the detection sensitivity of microfluidic chip with contactless conductivity detection was successfully applied to the determination of galantamine in human plasma.It reduces the conductivity of background buffer,increases the difference between the conductivity of background detection and the conductivity of substance to be measured,then greatly improves the sensitivity of contactless conductivity detection.It was carried out by adding 20%ethanol in the running buffer.The other optimized detection conditions were the same as those of galantamine hydrobromide tablet detection.Using this method,the sensitivity enhancement factor reached 580.