Study On The Methods For Simultaneously Determining Anti-anginal Drugs Of Diltiazem, Metoprolol And Isosorbide Mononitrate In Human Serum

The analysis of blood samples is very important in pharmacokinetic study and clinical blood drug concentration monitoring. Because some problems exist in analysis of blood samples, such as the composition of blood samples are complex; the preparation of blood samples are difficult; the concentration of drugs in blood samples are low, the analysis of blood samples are difficult. However, the concentration of drugs in blood samples is very important to investigate the process in vivo and build individual treatment plan. In this paper, we built methods to separate and determine simultaneously isosorbide mononitrate, metoprolol tartrate and diltiazem hydrochloride in human serum by micellar per anqueous liquid chromatography, capillary electrophoresis and capillary gas chromatography, and we validated these methods and the concentration of these drugs in human serum samples have been determinate. The major works in this paper are as follows:1) A novel micellar liquid chromatography was built to separate and determine simultaneously isosorbide mononitrate, metoprolol tartrate and diltiazem hydrochloride in human serum. We investigrated the influences on chromatographic behavior in simultaneous separation isosorbide mononitrate, metoprolol tartrate and diltiazem hydrochloride, such as the types of stationary phase, pH, the kinds of organic solvent and its volumn ration, column temperature.2) We proposed firstly a novel method-micellar per anqueous liquid chromatography based on micellar liquid chromatography, which avoid the distdvantage of low sensitivity in micellar liquid chromatography. According to the experiment results, we study the separation mechanism of micellar liquid chromatography and micellar per anqueous liquid chromatography, and built a separation model to show intuitively the separation process. In theory, the similar and difference of both methods has been contrasted, and the reason of the sensitivity improvement has been explained.3) A novel capillary electrophoresis combining on column field-amplified sample stacking was built to separate and determine simultaneously isosorbide mononitrate, metoprolol tartrate and diltiazem hydrochloride in human serum. We investigrated the influences on chromatographic behavior in simultaneous separation isosorbide mononitrate, metoprolol tartrate and diltiazem hydrochloride, such as the kinds and the concentration of buffer sult in back-ground electrolyte, pH, and voltage in sepration; the concentration of H3PO4, the kinds and the volumn ration of organic solvent in samples; the length of water plug the time and voltage in the electromigration injection. According to the experiment results, we study the separation mechanism of capillary electrophoresis combining on column field-amplified sample stacking, and built a separation model to show intuitively the separation process.4) A novel capillary gas chromatography was built to separate and determine simultaneously isosorbide mononitrate, metoprolol tartrate and diltiazem hydrochloride in human serum. We investigrated the influences on chromatographic behavior in simultaneous separation isosorbide mononitrate, metoprolol tartrate and diltiazem hydrochloride, such as the temperature of oven, the pront injection and the pront detection, and the injection volume and split ratio, the derivatization time of analytes.