Ethyl glucuronide : a new biochemical marker for acute alcohol intake : studies on possible causes for false-negative or false-positive results

In recent years, there has been a growing interest in various biochemical markers for detecting acute and chronic alcohol consumption. Biochemical markers for acute and chronic drinking play important roles in detecting alcohol use, abuse and dependence in hospital settings, work place settings, traffic medicine and in forensic toxicology examinations. The alcohol biomarkers can be distinguished into two main classes: 1) tests that are sensitive enough to detect a single intake of alcohol, such as ethanol, 5-hydroxytryptophol(5HTOL), ethyl glucuronide (EtG) and ethyl sulfate (EtS), and 2) tests that are able to detect chronic heavy drinking, or indicate body organ or tissue damage caused by long-term exposure to alcohol, such as carbohydrate-deficient transferrin (CDT), g -glutamyl transferase (GGT), aspartate and alanine aminotransferase (AST and ALT), and the mean corpuscular volume of erythrocytes (MCV). After consumption of alcoholic beverages, a small portion (95%) instead becomes metabolized mainly in the liver in a two-stage oxidation process, first to acetaldehyde by alcohol dehydrogenase and further to acetate by aldehyde dehydrogenase. Another very small part undergoes non-oxidative metabolism to produce the phase II products EtG and EtS. The interest in EtG and EtS as biochemical markers for acute alcohol intake has primarily focused on the observation that the washout rates for these direct ethanol metabolites are much slower than for the parent compound, allowing for a longer detection time (i.e., higher sensitivity). A positive finding of EtG and/or EtS in urine or serum thus provides a strong indication that the person was recently drinking alcohol, even if drinking is denied and also for some time after ethanol itself is no longer detectable. The purpose of this thesis was to evaluate the accuracy of EtG in urine as a biochemical marker for acute alcohol consumption, by studying possible sources of error that can affect the result of the analysis and cause false-negative or false-positive results. Urinary EtG was determined by liquid chromatography-mass spectrometry (LC-MS). The first study demonstrated that glucuronide conjugation of ethanol forming EtG represents a minor elimination pathway (