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Studies on Detection of Minor Metabolites of Ethanol and Ethyl Glucuronide Metabolism in Chinese Population

Author: ZhaoZuo
Tutor: ZhuoXianYi
School: Fudan University
Course: Forensic
Keywords: Ethyl glucuronide Metabolism and Pharmacokinetics Gas chromatography - mass spectrometry Liquid chromatography - mass spectrometry LTQ-Orbitrap
CLC: D919.2
Type: Master's thesis
Year: 2010
Downloads: 58
Quote: 0
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Abstract


Wine culture has a long history in China, has become a serious social problems caused by drinking accidents and cases. Technical appraisal of the alcohol-related, such as the identification of drink driving or drunk driving, drinking and hit and run identified corpses alcohol source determination, etc., are often faced with the problem of the forensic work. 95% -98% of the intake of ethanol into the human body by the liver metabolism, is first oxidized to acetaldehyde and further oxidized to acetic acid; remaining part (2% -5%), mainly original morphology by urine , excreted in the breath and sweat; only trace the wakes (lt; 0.1%) and uridine-5'-diphosphate - glucuronide to produce ethyl glucuronide (Ethyl Glucuronide, Et ( ?) G) excreted from the sample; simultaneously the trace ethanol metabolism in the liver into ethyl sulfate esters (Ethyl Sulphate, EtS) excreted in the urine. Ethyl glucose glucuronide and ethyl sulfate residence time in the body longer than its original body ethanol, in recent years, more and more people are seriously be considered iconic compounds ethanol. Undetectable blood ethanol in a drunk driving accident, hit and run cases, when, detected certain amount of ethyl glucuronide and ethyl sulfate, can also be considered to be driving under the influence or alive photo into ethanol. Dynamics abroad have been some reports about the testing and in vivo metabolism of ethyl glucuronide, the domestic yet reported. The this thesis ethyl glucuronide as the main object of study, is committed to the establishment of the blood and urine ethyl glucuronide qualitative, quantitative analysis method, and the method detection limit, recovery, linearity range wine and other Chinese people to evaluate timing determination of blood and urine ethyl glucuronide concentration; healthy volunteers control dose after drinking, investigated the metabolic dynamics of the Chinese people in vivo glucose ethyl glucuronide; determine After ethyl glucuronide time limit of detection; initially realized the blood EtG and ethanol concentration relationship presumption drinking time data modeling. All content in accordance with the work carried out in chronological order is divided into six chapters. The first chapter introduces the research progress and application of domestic and foreign EtG analysis on the research background, significance and major work. The second chapter of the establishment and evaluation of gas chromatography - tandem mass spectrometry (GC-MS/MS) method of measuring blood EtG. This method the blood EtG limit of detection (LOD) 0.05μg/mL, the the linear range 0.1μg/mL-10μg/mL (R2 = 0.9999), the accuracy of 90% -110%, intra-day precision and day between precision were less than 15%, and successfully applied to the detection of the actual case. Chapter and evaluation of a liquid chromatography - linear ion trap - orbit ion trap (LC-LTQ-Orbitrap) the method of determination of blood and urine EtG. The method of blood, urine EtG detection limit are 0.02μ/mL, linear range 0.05-5.00μg/mL (R2 gt; 0.998), two matrix EtG detection the intraday accuracy day accuracy are 85% -110%, intra-day precision and inter-day precision were less than 10%. Chapter and evaluation of liquid chromatography - tandem mass spectrometry (LC-MS/MS) method of determination of blood and urine EtG. The methods of blood and urine EtG detection limit are 0.05μg/mL, and the linear range 0.1μg/mL-5μg/mL (R2 gt; 0.999), the two matrix EtG detection method accuracy was 95 days % -105%, intra-day precision and inter-day precision were less than 15%. Chapter conducted dose in healthy volunteers controlled drinking experiment, collect blood and urine samples; LC-MS/MS method using the established test samples, visits EtG metabolic dynamics of the blood and urine of EtG in blood relationship between ethanol and urine. The statistical software Stata 7.0 calculation, EtG in blood concentration peak for 4-6h, the detect time limit for 8-21h, the long time limit of detection than blood ethanol 8-10h. Ethanol EtG in urine concentration peak for 4-6h, the detection time limit for 20-85h, ethanol than urine detection time limit a length of 12-70h, and thus initially established a projected the drinking time data model by EtG and ethanol concentration. Chapter VI established the blood and urine EtS LC-LTQ-Orbitrap analysis method. Linear range 0.1μg/mL-5μg/mL (R2 gt; 0.995). In this study, in the country for the first time established a GC-MS/MS, LC-LTQ-Orbitrap and LC-MS/MS EtG detection methods and method validation, LC-LTQ-Orbitrap international reported; first expedition to Chinese people drink ethyl glucuronide metabolic dynamics, and to explore the relationship of blood and urine EtG and ethanol, EtG time limit of detection in the blood, urine. The research results for drink driving to escape identification, ethanol sources cadaveric samples provide a scientific basis for judgment.

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