| This thesis mainly established analytical methods for determination glucosamine, telmisartan, dolasetron and its metabolite, hydrodolasetron in human plasma by high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC/ESI-MS). The results provided a guideline for the development and design of new drugs, and reliable data for clinical application and pharmacokinetics study. The ionization efficiency of these drugs was investigated and the optimized experiment condition was concluded. Besides, we made some preliminary study on ionization efficiency of ESI. When ionization efficiency was improved, the sensitivity of the method was much higher. This study could provide a guideline for selecting suitable structure of analyte, instrument parameters and solvent parameters for HPLC/ESI-MS.This thesis has mainly finished the following work:1. An analytical method was developed for the determination of glucosamine in human plasma by high performance liquid chromatography/electrospray-mass spectrometry. Analytes were reacted with PITC after albumen precipitation with acetone, which improved the retention and ionization efficiency of glucosamine by adding a hydrophobic group to the structure of glucosamine. The condition of experiment was investigated, such as amount of PITC, reaction time, temperature etc. High sensitive ESI-MS detector was selected to determine glucosamine in the human plasma, and this method was successfully applied to the bioequiavailability and pharmacokinetics study.2. A HPLC/ESI-MS method was developed for determination of telmisartan in human plasma. Different organic solvent was investigated for albumen precipitation in our experiment. Plasma sample was injected to HPLC/ESI-MS directly after albumen precipitation with acetronitrile. High sensitive ESI-MS detector was selected to determine telmisartan in the human plasma, and this method was successfully applied to the bioequiavailability and pharmacokinetics study.3. Dolasetron and its metabolite hydrodolasetron were determined with high performance liquid chromatography/electrospray-mass spectrometry in human plasma simultaneously. Analytes were extracted from plasma sample by induced phase transition extraction, and extracted efficiency was all more than 95% for analytes. Besides, the upper layer could be used as injection solution without further purification and interference of backgrounds was lower than that of other sample pretreatment methods. High sensitive ESI-MS detector was selected to determine dolasetron and hydrodolasetron in the human plasma, and this method was successfully applied to the pharmacokinetics study. 4. The factors that effect ionization efficiency of electrospray ionization, including the structure of analyte, instrumental parameter and solvent parameter, were investigated. What was suitable for analyzing with ESI-MS was determined by the structure of analyte. For what was not suitable for ESI-MS analysis, it could be improved by modification of structure. Instrument parameter could be optimized to be the best and ESI ionization efficiency could be improved by changing solvent parameters such as surface tension, volatility, etc. In this section we have made some preliminary study of ESI ionization and application in practical analysis.
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