Flow-injection Chemiluminescence Detection And Capillary Electrophoresis Analysis For Studying Metabolism Of Unbound Medicines And Metal Ion

In recent years, microdialysis sampling has been an important role in the area of pharmacokinetics, especially in the research of distribution and metabolism of drugs. Microdialysis sampling can be coupled to many analytic techniques, among these techniques HPLC with various detection systems was widely used. However, HPLC does have certain disadvantages, namely long separation times and a requirement for relatively large injection volumes which result in relatively low time resolution, high consumption, these disadvantages limit it's use in pharmacokinetics. Capillary electrophoresis is a relatively new technique of separation and quantitation; theoretically, it presents numerous advantages for application in pharmacokinetics: low sample volume injected, high separation efficiency, low consumable expense and relatively simple process of sample preparation. The technique of flow-injection chemiluminescence analysis has been widely used as detection method for its advantages: high sensitivity, rapid, wide linear range, the instrumentation used was relatively simple, low cost and easy to minimize.Objective: (1) To couple microdialysis sampling with capillary electrophoresis for real time and on-line detection of concentration of free drugs in the blood of rabbit; (2) To couple microdialysis sampling with flow-injection chemiluminescence analysis for real time and on-line detection of concentration of free Cr(III) in the blood of rabbit.Method: (1) Firstly, optimize electrophoretic conditions (including the nature, pH and ionic strength of buffer; the injection mode and volume; applied voltage) to achieve separation of objective drug and internal standard. Linearity, reproducibility, and recovery of the method were tested. Secondly, optimize microdialysis system (including the nature of perfusate and perfusate flow rate) and determine dialytic efficiency under optimized conditions. Thirdly, real-time, on-line determine the metabolism of tested medicine in rabbit blood using the microdialysis-CE system. (2) Firstly, optimize of CL system (including the...