Mass spectrometric identification of ethyl sulfate as an ethanol metabolite in humans.

Abstract

After alcohol ingestion, the bulk of ethanol ingested (≥95%) is rapidly eliminated in the liver in a two-stage oxidation process: first to acetaldehyde by alcohol dehydrogenase and then to acetic acid by aldehyde dehydrogenase. The remainder is excreted mainly unchanged in urine and expired air. However, another small fraction of the ingested ethanol dose (<0.1%) (1) undergoes a phase II conjugation reaction catalyzed by UDP-glucuronosyltransferase (UGT) to produce ethyl glucuronide (EtG), which is eventually excreted in the urine (2)(3)(4). Because EtG has a longer period of elimination than the parent compound, the interest in EtG has largely focused on its use as a sensitive and specific biomarker of recent alcohol intake with clinical and forensic applications (5)(6). Animal studies have indicated that ethanol may also undergo sulfate conjugation through the action of sulfotransferase to produce ethyl sulfate (EtS) (7)(8)(9). After an oral dose of ethanol and injection of 35S-labeled sulfate in rats, EtS was apparently excreted in urine mainly during the first 24 h (10). However, a general limitation in these studies was the lack of reliable methods for unequivocal identification of EtS and precise quantification. In the present study on humans, we used a sensitive and specific liquid chromatographic–mass spectrometric (LC-MS) method to determine whether EtS is formed after …