Ethyl Glucuronide: A biomarker for Acute Alcohol Ingestion

Ethyl glucuronide (EtG) along with ethyl sulfate (EtS) test validity are commented on. Sensitivity, specificity and reference threshold levels for urine screen are outlined. The accidental ingestion and absorption of ethanol from household products are also discussed. Ethyl glucuronide, a biochemical marker for ethanol, is a useful screen after acute alcohol ingestion, whether intentional or accidental. Keywords: Ethyl Glucuronide, Biomarkers, Ethanol, Alcohol ingestio

Data on ethyl glucuronide and cocaethylene concentrations in the hair of cocaine users.

We present data on ethyl glucuronide and cocaethylene concentrations from the hair of cocaine users. Head hair from 64 subjects, previously tested for cocaine, cocaethylene, benzoylecogonine and anhydroecgonine methyl ester (AEME), were subsequently analysed for Ethyl Glucuronide (EtG). Samples were prepared by solid phase extraction and analysed using gas chromatrography coupled to tandem mass spectrometry. The dataset is made available to allow analysis of possible correlation between cocaethylene and ethyl glucuronide or between other metabolites presented in the data

The effects of zinc sulfate on ethyl glucuronide immunoassay urine testing

Published research in the Journal of Analytical Toxicology and the American Society for Clinical Pathology has confirmed that the presence of Zinc Sulfate in adulterated urine samples can influence the testing results using EMIT and ELISA immunoassay testing when testing for Cannabinoids (THC), Cocaine (Benzoylecgonine), Methamphetamines, Opiates (Morphine, Methadone, and Propoxyphene), Phencyclidine (PCP), and Ethanol (Alcohol Dehydrogenase). This research included adding Zinc Sulfate directly to urine samples. In 2006, the Substance Abuse and Mental Health Service Administration (SAMHSA) released an advisory that the use of Ethyl glucuronide (EtG) as a new biomarker as an indicator for the past-use of alcohol was promising and warranted more research. Ethyl glucuronide is a direct metabolite of the biotransformation of ethanol in the human body. This compound is excreted in urine and can be used as a specific biomarker for the ingestion of alcohol. Because EtG is only produced when ethanol is metabolized, there are no false positives due to fermentation and a much longer detection window exists for its detection. Scientific literature states that EtG can be present in urine long after ethanol has been eliminated. Testing for EtG is commonly referred to as the “80 hour test” for the ability of EtG to be measured up to 80 hours after consuming alcohol. It was hypothesized that if the presence of Zinc Sulfate added to urine falsely reduced urine alcohol level when measuring for Alcohol Dehydrogenase enzyme, will the presence of Zinc Sulfate added to SurineTM falsely reduce the urine alcohol level when measuring for EtG? Since it is very likely that EtG would still be present in the body after ethanol has been eliminated, samples contained either no ethanol or 5% (5g/dL) of ethanol. Samples were spiked at 10mg/mL, 15mg/mL or contained 0mg/mL of Zinc Sulfate. Additionally, duration testing was conducted to see if there was any observed differences between testing the samples fresh and then after a one week duration in a refrigerator and brought to room temperature prior to testing. Two different immunoassay EtG tests were used to perform the analysis. It was concluded that Zinc Sulfate directly added to the sample affected one of the immunoassay test regardless of whether EtG or ethanol were present, by fading the Test and Control regions. Additionally, it is concluded that SurineTM samples containing Zinc Sulfate could easily be distinguished from samples free of Zinc Sulfate because of the presence of a white cloudy precipitate

Diagnostic performance of ethyl glucuronide in hair for the investigation of alcohol drinking behavior: a comparison with traditional biomarkers

Background: Ethyl glucuronide (EtG) in hair has emerged as a useful biomarker for detecting alcohol abuse and monitoring abstinence. However, there is a need to establish a reliable cutoff value for the detection of chronic and excessive alcohol consumption. Methods: One hundred and twenty-five subjects were classified as teetotalers, low-risk drinkers, at-risk drinkers, or heavy drinkers. The gold standard for subjects' classifications was based on a prospective daily alcohol self-monitoring log. Subjects were followed for a 3-month period. The EtG diagnostic performance was evaluated and compared with carbohydrate-deficient transferring (CDT) and the activities of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl-transferase (γGT). Results: A cutoff of >9pg/mg EtG in hair, suggesting an alcohol consumption of >20/30g (at-risk drinkers), and a cutoff of >25pg/mg, suggesting a consumption of >60g (heavy drinkers), were determined by receiver operating characteristic analysis. The EtG diagnostic performance was significantly better (P < 0.05) than any of the traditional biomarkers alone. EtG, as a single biomarker, yielded a stronger or similar diagnostic performance in detecting at-risk or heavy drinkers, respectively, than the best combination of traditional biomarkers (CDT and γGT). The combination of EtG with traditional biomarkers did not improve the diagnostic performance of EtG alone. EtG demonstrated a strong potential to identify heavy alcohol consumption, whereas the traditional biomarkers failed to do so. EtG was not significantly influenced by gender, body mass index, or age. Conclusion: Hair EtG definitively provides an accurate and reliable diagnostic test for detecting chronic and excessive alcohol consumption. The proposed cutoff values can serve as reference for future cutoff recommendations for clinical and forensic us

ETHYL GLUCURONIDE: A BIOMARKER TO IDENTIFY ALCOHOL USE BY HEALTH PROFESSIONALS RECOVERING FROM SUBSTANCE USE DISORDERS

Aims: Physicians recovering from substance-related disorders are usually allowed to return to practice if they agree to remain abstinent from drugs, including alcohol, and to undergo random urine testing. Over 9000 physicians are currently involved in such monitoring programs in the US. To date, it has been difficult to adequately monitor abstinence from alcohol due to the short half-life of alcohol and no other highly specific marker. Ethyl glucuronide (EtG), a direct metabolite of alcohol, offers an extended window for assessment of drinking status (up to 5 days). Our aim was to assess the potential value of EtG testing in abstinence-based monitoring programs. Patients and methods: Urine samples were obtained from 100 participants in a physician monitoring program and additional samples were subsequently obtained ‘for cause', ‘to verify positive urine alcohol, when drinking was denied' and ‘in high risk individuals'. All participants had signed contracts agreeing to remain abstinent from mood-altering drugs, including alcohol, and had agreed to random urine testing. EtG was determined using LC/MS-MS in addition to standard testing. The main outcome measure were urine specimens positive for EtG versus those positive based on standard testing for alcohol and other drugs. Results: Among the initial 100 random samples collected, no sample was positive for alcohol using standard testing; however, seven were positive for EtG (0.5-196 mg/l), suggesting recent alcohol use. Subsequent EtG testing was performed clinically during the course of monitoring. Of the 18 tests performed to date, eight of eight tests performed ‘for cause' were positive for EtG but negative for all other drugs including urine alcohol. All eight were confirmed positive by self reported drinking by the patient when confronted regarding the positive test result. Of six tests performed to ‘confirm a positive urine alcohol' two were positive for EtG and confirmed positive by self reported drinking. For the other four samples, especially as two are from a diabetic, in vitro fermentation of ethanol is discussed. Conclusions: These data suggest that physicians in monitoring programs have a higher rate of unrecognized alcohol use than previously reported. Incorporation of EtG testing into alcohol abstinence monitoring can strengthen these program

Ethylglucuronide replacing ethanol in the routine screening of alcohol dependent outpatients: clinical implications

[eng] BACKGROUND: The development of an alcohol biomarker is a long process where different stages take place over time. From discovery to full clinical use and implementation, each accomplished stage increases the confidence in and the relevance of such biomarkers. In recent years, new biomarkers have been discovered, with outstanding improvements in the sensibility and specificity for the detection of recent drinking. However, the clinical, therapeutic and economical consequences of such biochemical improvements remain to be determined. With the present thesis we expect to investigate the clinical implications of such new biomarkers, with a special focus on urine ethyl glucuronide (EtG), in order to fully establish its contribution to the field of alcohol use disorders. It comprises three articles: the first (Study 1) compares the screening performance of ethyl glucuronide versus ethanol, clinical judgment and self report, under routine, real circumstances in alcohol dependent outpatients. The second one (Study 2) investigates the differential, one-year clinical evolution of patients screening positive and negative in Study 1, taking into account both clinical and economic consequences. Finally, Study 3 evaluates patients’ knowledge and attitudes towards regular alcohol urine screening. METHODS: Study 1 consisted of a cross-sectional comparison aiming at clinically validating EtG under real, routinely clinical conditions. For that purpose, 613 consecutive urinary samples, provided by 188 outpatients with alcohol dependence were analyzed for ethanol and EtG. Study 2 retrospectively assessed the clinical evolution of patients participating in Study 1. A survival analysis was conducted in order to compare the rate of relapse between EtG positive and negative patients. Regression models were performed to compare the mean number of days hospitalized between groups, the risk of being lost to follow-up and treatment expenses. In Study 3 a cross-sectional survey among alcohol dependent outpatients was conducted. In consonance with the principles of patient centered care, it aimed at investigating patients’ attitudes and beliefs towards regular alcohol urine screening. For attitudes’ assessment, we adapted the Drug Attitude Inventory (DAI-10) to the field of alcohol urine screening. Internal consistency, test-retest reliability and concurrent validity were evaluated for the adapted questionnaire. RESULTS: Study 1 showed an overriding superiority of EtG over ethanol, clinical judgment and self report, detecting a significant greater number of positive samples in routine, real circumstances. Study 2 revealed a clearly different clinical evolution between EtG positive and negative patients during the following 12 months, with EtG positive patients being at greater risk of relapse, hospitalization and incurring in more treatment expenses. Study 3 suggested that regular alcohol screening is highly valued by alcohol outpatients. It also showed that besides relapse prevention, other functions related to therapeutic alliance building, social desirability and impression management play a key role as well. CONCLUSIONS: Regular alcohol urine screening with ethyl glucuronide seems to have an impact on the clinical management of alcohol dependent outpatients, offering a better detection of recent drinking and the possibility of an improved relapse prevention strategy.[spa] INTRODUCCIÓN: El desarrollo de biomarcadores para el consumo de alcohol es un proceso largo y laborioso, donde múltiples etapas se suceden en el tiempo. Desde su descubrimiento en el laboratorio hasta su total implementación clínica, cada etapa superada incrementa la confianza y la relevancia de dicho marcador. En los últimos años se han descubierto marcadores que cuentan con una notable sensibilidad y especificidad en cuanto a la detección de consumo reciente se refiere. Sin embargo, las implicaciones clínicas, terapéuticas y económicas de dichos marcadores todavía no han sido esclarecidas con total claridad. Con la presente tesis se pretende investigar las implicaciones clínicas de dichos nuevos marcadores, específicamente del etilglucurónido (EtG), con el objetivo de determinar su verdadera aportación al campo de los trastornos por uso de alcohol. Esta tesis está compuesta de tres artículos. El primero (Estudio 1) compara el rendimiento en el cribado de consumo de alcohol del etilglucurónido frente al etanol, el juicio clínico y el autoinforme, bajo condiciones rutinarias y reales en pacientes dependientes del alcohol ambulatorios. El segundo artículo (Estudio 2) investiga la evolución clínica diferencial entre los pacientes que obtuvieron un resultado positivo y uno negativo en el Estudio 1, durante los siguientes 12 meses. Finalmente, el tercer artículo (Estudio 3) evalúa los conocimientos y la actitud que los pacientes presentan ante el cribado rutinario de alcohol. MÉTODOS: El Estudio 1 consistió en una comparación transversal cuya finalidad fue la de evaluar el uso de EtG bajo condiciones clínicas rutinarias de elevada validez externa. Para ello 613 muestras de orina consecutivas, proporcionadas por 188 pacientes ambulatorios con dependencia al alcohol, fueron analizadas para etanol y etilglucurónido. El Estudio 2 evaluó retrospectivamente la evolución clínica de los participantes del Estudio 1. Se llevó a cabo un análisis de supervivencia con el fin de comparar la tasa de recaída entre pacientes con un resultado positivo y negativo a etilglucurónido. Se realizaron análisis de regresión para comparar entre grupos el número medio de días hospitalizados, el riesgo de abandonar tratamiento y los costes medios del tratamiento. En el Estudio 3, en consonancia con los principios de la medicina centrada en el paciente, se realizó una encuesta a pacientes con dependencia del alcohol ambulatorios con la finalidad de evaluar sus actitudes, creencias y conocimientos en relación al cribado rutinario de alcohol en orina. Para la evaluación de sus actitudes se adaptó la escala Drug Attitude Inventory (DAI-10), analizándose su consistencia interna, su fiabilidad test-retest y su validez concurrente. RESULTADOS: El Estudio 1 mostró una clara superioridad del EtG sobre el etanol, el juicio clínico y el autoinforme, detectando un mayor número de positivos en condiciones reales de elevada validez externa. El Estudio 2 demostró una clara y diferente evolución clínica entre los pacientes que fueron EtG positivo y EtG negativo durante los siguientes 12 meses, presentando los pacientes EtG positivo un mayor riesgo de recaída, de hospitalización así como mayores costes de tratamiento. El Estudio 3 sugirió que el cribado rutinario de alcohol en orina es percibido por los pacientes dependientes al alcohol como un elemento valioso de su tratamiento. Se observó también que, además de cumplir una función de prevención de recaídas, otras funciones relacionadas con el vínculo terapéutico, la conveniencia social y la gestión de impresiones juegan también un papel clave. CONCLUSIONES: El cribado rutinario de alcohol mediante EtG parece tener un impacto en el manejo de los pacientes dependientes al alcohol ambulatorios, ofreciendo una mejor detección del consumo reciente de alcohol así como la posibilidad de una mejor prevención de recaídas

Alcohol Consumption during Pregnancy : Analysis of Two Direct Metabolites of Ethanol in Meconium

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26-34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0-110.6 ng/g). With respect to EtS, it was undetectable (<0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health