Ethyl Glucuronide and Ethyl Sulphate in Urine: Caution in their use as markers of recent alcohol use

Abstract

Aim To clarify the role of the ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), in monitoring alcohol consumption. Method We recruited 7 female and 17 male volunteers who were instructed to consume a quantity of beer (containing 48 gm ethanol) with food in one session. We examined urinary excretion of EtG and EtS over time and looked for correlations between the concentrations of the metabolites EtG and EtS. Results EtG concentrations in urine varied between 0.026 and 430.372 μg/ml with average values between 11.85 μg/ml (SD 19.75), 30 min after alcohol intake, and 100.39 μg/ml (SD 101.34), 4.5 h after alcohol intake. EtS urinary concentration ranged from 0.006 to 101.432 μg/ml with average values between 4.77 μg/ml (SD 5.42), 30 min after alcohol intake, and 30.14 μg/ml (SD 27.20), 4.5 h after alcohol intake. Spearman’s test showed that urinary EtG and EtS correlated significantly at several time points. Conclusion The great interindividual variability in their excretion suggests caution in the use of urinary measurement of these metabolites in forensic investigations.

Biomarkers of moderate alcohol intake and alcoholic beverages: a systematic literature review

“…In another study showing dose–response, the apparent time window for EtG in the serum was 25–50 h, depending on alcohol dose, with the lowest dose tested being ~ 25 g (2–2½ units) [ 57 ]; no background level above the method cutoff for EtG could be measured after 1 week of abstaining. In a recent study, there was a high variability in the peak level and total EtG excretion in 24 volunteers after drinking 48 g of alcohol as beer [ 58 ]. Inter-individual variation in peak serum levels of EtG (at 10–20 h) and time to reach plasma levels below LOQ (range: 35–100 h) has been reported after binge-drinking of 64–172 g alcohol within 6 h [ 59 , 60 ].…”

“…The time-response in 13 volunteers was also investigated after consumption of a low alcohol dose (0.1 g/kg body weight) showing a peak at 2–5 h and a time window of detection of 6–10 h; preliminary indication was also shown of a higher fractional as well as total excretion at a 5 times higher dose (time window ≥ 24 h) [ 80 ]. In a recent study, in 24 male and female volunteers provided with 47.5 g alcohol (beer) within 15 min, the inter-individual variability in EtS excreted over 10.5 h was more than 100-fold at the excretion peak apex and with a variable peak time of 2.5–8.5 h [ 58 ]. EtS showed considerable correlation with measured levels of EtG before as well as after the drink.…”

“…In this study, one of the volunteers hardly produced any EtS or EtG after drinking 47 g of alcohol in 15 min, while a few others only showed very low levels, indicating that these markers may miss a small percentage of drinkers. ADH genotyping was not provided, but the authors suggest polymorphic phase 2 enzymes to be the main cause of this variability [ 58 ]. However, this is less likely considering the high correlation between the EtS and EtG markers.…”

Dietary ethanol ingestion by free-ranging spider monkeys (Ateles geoffroyi )

“…In humans, ethanol consumption typically yields elevated EtG and EtS levels for a number of days [ 21 , 22 ]. And for any given rate of consumption, urinary concentrations of both metabolites are strongly dependent on individual identity [ 23 ]. No relevant data exist for non-human primates that would enable the correlation of the EtG and EtS concentrations reported here to rates of ethanol ingestion, or to any behavioural or physiological consequences of such ingestion.…”

Rapid and simple LC–MS/MS determination of urinary ethyl glucuronide, naltrexone, 6β-naltrexol, chlordiazepoxide, and norchlordiazepoxide for monitoring alcohol abuse

“…Therefore, clear criteria are required to avoid misidentification of unintentional alcohol exposure as alcohol consumption (Substance Abuse and Mental Health Services Administration 2012b; McDonell et al 2015). The cutoff value of urinary EtG has been proposed to confirm alcohol consumption, which cannot be implemented for other alcohol biomarkers (Mercurio et al 2021). The Substance Abuse and Mental Health Services Administration (SAMHSA) of the United States government has categorized the amount of urinary EtG detected as high positive (> 1,000 ng/mL), low positive (500-1,000 ng/mL), or very low positive (100-500 ng/mL) (Substance Abuse and Mental Health Services Administration 2012a).…”