Ethyl glucuronide: On the time course of excretion in urine during detoxification

Universität Ulm, Ulm, Baden-Württemberg, Germany
Addiction Biology (Impact Factor: 5.36). 10/2002; 7(4):427-34. DOI: 10.1080/1355621021000006035
Source: PubMed


Ethyl glucuronide (EtG) is a promising new biological state marker of recent alcohol consumption that detects alcohol use reliably over a definite time period. Other currently available markers lack acceptable sensitivity and specificity. Our aim is to elucidate under naturalistic conditions the time course of EtG excretion in urine following alcohol consumption and to show how this can be utilized for monitoring and prognosis in patients. There are no other existing data on this issue to date. One hundred and thirty-eight urine samples from 28 male alcohol withdrawal patients were drawn every 3-24 hours for up to 94 hours after hospitalization. Breath ethanol concentration (mean) at hospitalization was 900 mg/L. Patient age in years was 40.3 (mean). Determination of urine EtG was performed by gas chromatography/mass spectrometry (GC/MS) with deuterium-labelled EtG as an internal standard. The strongest correlations (p<0.01) were found between EtG determinations in the different patient when breath ethanol concentrations (BEC) were 0 and 48 hours after BEC=0 (r=0.747), EtG 24 and 48 hours after BEC=0 (r=0.872), and in the time frame of detection (hours) of EtG and EtG 48 hours after BEC=0 (r=0.762). No significant correlation was found (Mann-Whitney test) between EtG concentrations in urine at different time points between the groups of patients with (a) 1 or less-2, (b) 3-4 or more previous hospitalizations, (c) a history of seizures (yes/no) or (d) an age above or below the median (40.5). EtG excretion in urine is not random, but seems rather to follow a kinetic profile. Furthermore our preliminary data indicate, that there is no significant difference for EtG concentration in urine when correlated to group variables such as age, seizures and hospitalizations.

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    • "In alcoholic patients followed during detoxification, detection times up to ∼80 h were initially reported (Wurst et al., 1999) and even longer times were found in a more recent study (Beck et al., 2007). Still, a study of 23 alcoholic patients during detoxification suggested a typical detection time of only ∼48 h after the ethanol had been eliminated (Wurst et al., 2002). The results of the present study demonstrated highly variable inter-individual detection times for EtG after admission to the hospital, ranging from ∼40 h up to ∼130 h. "
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    ABSTRACT: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugated ethanol metabolites formed in low amounts after alcohol consumption. Compared with ethanol, EtG and EtS are excreted in urine for a prolonged time, making them useful as sensitive alcohol biomarkers. This study determined the detection times for EtG and EtS in alcoholic patients undergoing alcohol detoxification. Alcohol-dependent patients (n = 32) with an initial alcohol concentration >or=1 g/L based on breath testing were followed during detoxification. Urine samples for determination of EtG, EtS, ethanol and creatinine were collected on admission to the hospital and thereafter once daily for several days. EtG and EtS measurements were performed by liquid chromatography-mass spectrometry (LC-MS) and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics). The detection time for urinary EtG was weakly correlated (r = 0.434, P = 0.013) with the initial alcohol concentration (range 1.0-3.4 g/L). For EtG, the individual time range until return to below the applied cut-off limit (<0.5 mg/L) was approximately 40-130 h (median 78) with a similar time course observed for EtS. After correction for urine dilution, the time until an EtG/creatinine ratio <0.5 mg/g was approximately 40- 90 h (median 65). The detection times after an estimated zero ethanol concentration were approximately 30-110 h (median 66) for EtG and approximately 30- 70 h (median 56) for EtG/creatinine. The EtG results by LC-MS and the immunoassay were in good agreement. During alcohol detoxification, EtG and EtS remained detectable in urine for several days. The detection times showed wide inter-individual variations, also after adjusting values for urine dilution and to the estimated times for a completed ethanol elimination.
    Preview · Article · Nov 2008 · Alcohol and Alcoholism
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    • "EtG and ethyl sulphate (EtS), another recently discovered human phase-II ethanol metabolite (Helander and Beck, 2004), are minor metabolites each making up less than 0.05% of the ingested ethanol dose (Dahl et al ., 2002; Helander and Beck, 2005), but they show much longer detection times than the parent compound (Borucki et al ., 2005; Hoiseth et al ., 2007). After the ethanol has been eliminated from the body, EtG and EtS remain measurable in the urine for another ∼1–4 days in a dose-dependent manner (Schmitt et al ., 1997; Dahl et al ., 2002; Wurst et al ., 2002; Borucki et al ., 2005). The resulting high sensitivity for recent alcohol consumption is the basis for their increasing popularity as alcohol biomarkers in clinical and forensic applications (Bergström et al ., 2003; Wurst et al ., 2003; Jones, 2006; Hoiseth et al ., 2007). "
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    ABSTRACT: The minor ethanol metabolite ethyl glucuronide (EtG) is used as a sensitive and specific test for recent alcohol consumption with clinical and forensic applications. This study evaluated a new enzyme immunoassay (DRI-EtG EIA, Microgenics Corp.) for determination of the EtG concentration in urine samples. Evaluation was done using the kit calibrators (range 0-5.0 mg/L) and controls, an external quality control sample, and 400 consecutive urines from the routine samples pool. The measuring range was extended by dilution of urine samples with saline. Comparison was made with an established liquid chromatographic-mass spectrometric (LC-MS) method. The intra- and inter-assay imprecision of the DRI-EtG EIA in the range 0.4-2.5 mg/L was <2.2% (coefficient of variation, CV), and the limit of quantification was <0.1 mg/L. For the 400 urine samples, the EtG concentrations obtained using the DRI-EtG EIA (mean 24.2 mg/L, range 0-830) and LC-MS method (mean 22.4 mg/L, range 0-959) showed an overall good and statistically significant agreement (r2 = 0.931, P < 0.0001). These results indicated a high level of accuracy and selectivity of the DRI-EtG EIA for quantification of urinary EtG. In the absence of a commonly accepted cut-off limit for urinary EtG, a threshold of 0.5 mg/L (2.2 mumol/L) is proposed, to obtain a high sensitivity but avoid positive results due to unintentional ethanol exposure.
    Preview · Article · Oct 2007 · Alcohol and Alcoholism
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    • "Because prolonged drinking does not cause accumulation of EtG in the body (Sarkola et al ., 2003), the longer detection times observed in this study most likely relate to the much higher doses of ethanol ingested. The detection times were also longer than those observed in a recent study of alcoholic patients (Wurst et al ., 2004), but in better agreement with reported detection times of up to 84 h in another study (Wurst et al ., 2002). An increased urinary GTOL/5-HIAA ratio was observed for between 9 and >96 h after admission, with a median value of 39 h (Fig. 1). "
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    ABSTRACT: This study compared two new methods for direct determination of 5-hydroxytryptophol glucuronide (GTOL) in urine, a biomarker for detection of recent alcohol consumption. Urine samples were collected from ten alcoholic patients during recovery from intoxication. A direct injection ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for measurement of the urinary GTOL to 5-hydroxyindoleacetic acid (5-HIAA) ratio, and an ELISA assay for direct measurement of GTOL, were used. Comparison was made with the urinary ethanol and ethyl glucuronide (EtG) concentrations. The breath ethanol concentration on admission ranged between 1.0-3.1 g/l. The UPLC-MS/MS method showed a median detection time of 39 h for an elevated urinary GTOL/5-HIAA ratio, while EtG was detected for a median of 65 h. Determination of GTOL by the ELISA assay showed 87% sensitivity in detecting positive samples at a 44% specificity, as compared with the UPLC-MS/MS method. The lower sensitivity of the urinary GTOL/5-HIAA ratio compared with EtG for recent drinking may be clinically useful, in cases where the EtG test provides an unwanted high sensitivity for intake of only small amounts of alcohol or unintentional ethanol exposure.
    Preview · Article · May 2007 · Alcohol and Alcoholism
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