Ethyl sulphate: a direct ethanol metabolite reflecting recent alcohol consumption

Background: Ethyl sulphate (EtS), a direct ethanol metabolite, appears to offer potential as a biomarker for recent alcohol consumption. Although its window of assessment is similar to that of ethyl glucuronide (EtG), there are differences between the two markers in their pathways for formation and degradation. Aims: (a) To assess the excretion of EtS compared to EtG and ethanol in drinking experiments with healthy volunteers, and (b) to elucidate the possibility of using the two metabolites for monitoring abstinence in substance use disorder patients during rehabilitation treatment. Design, setting, participants: (a) Nine drinking experiments were performed by six healthy volunteers (two females, four males), with a mean age of 34.1 years (2062), average oral intake of 0.2 g/kg ethanol (0.10.61), and having 74 spot urine samples. (b) Thirty-six substance abuse patients (mean age 41.9 years, 2059; 22 males, 14 females) in a rehabilitation programme after withdrawal, producing 98 urine samples. Ethyl glucuronide and ethyl sulphate were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) using d5-EtG and d5-EtS, respectively, as an internal standard. Findings: (a) Volunteers: EtG and EtS were detectable for up to 36 hours and reached the limits of determination in urine at 20.6 hours and 21.2 hours (median), respectively, after ethanol intake. EtG-100 (standardized to a creatinine of 100 mg/dl) reached its maximum level at 2.8 hours and EtS-100 at 2.1 hours (median) after the beginning of the experiment. Of the ethanol ingested, 0.022% was excreted as EtS in one volunteer. Eight samples were positive for EtS only and six for EtG only. Spearman's rank correlation coefficients of 0.84 (P < 0.0001) between EtG and EtS and 0.87 (P < 0.0001) between EtG-100 and EtS-100 were found. (b) Patients: of the 98 urine samples evaluated, 27 were positive for EtS and of these only 20 were also positive for EtG. Spearman's rank correlation coefficients of 0.84 (P < 0.0001) between EtG and EtS and 0.82 (P < 0.0001) between EtG-100 and EtS-100 were found. Conclusions: The data from patients and volunteers suggest that the direct ethanol metabolite ethyl sulphate has the potential to serve as a biomarker of recent ethanol intake. Because EtG and EtS are formed via different pathways they might be used conjointly, thereby increasing sensitivity. (Review' s abstract)