Time course and reproducibility of urinary excretion profiles of ethanol, methanol, and the ratio of serotonin metabolites after intravenous infusion of ethanol.
BACKGROUND
The aim of this study was to determine the time course and reproducibility of urinary excretion profiles of ethanol, methanol, and ratio of serotonin metabolites, 5-hydroxytryptophol (5HTOL) to 5-hydroxyindoleacetic acid (5HIAA), under strictly controlled conditions.


METHODS
Nine healthy volunteers (6 women and 3 men) received 0.40 g of ethanol/kg of body weight on two occasions by constant rate intravenous infusion 30 min. Urine was voided before administration of ethanol and thereafter every 60 min for a total of 8 hr. Concentrations of ethanol and methanol in urine were determined by headspace gas chromatography, and the serotonin metabolites 5HTOL and 5HIAA were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively.


RESULTS
The peak concentration of ethanol in urine occurred at 30 or 60 min after the infusion ended. The peak concentration of methanol and the 5HTOL/5HIAA ratio developed more gradually, reaching a plateau at 213 to 220 min and 200 to 220 min postinfusion, respectively. The concentration-time profiles of ethanol and the 5HTOL/5HIAA ratio varied more between subjects than within subjects (p < 0.001), whereas the inter- and intraindividual variation in the pharmacokinetics of methanol were not significantly different (p > 0.05). The concentration of methanol and the 5HTOL/5HIAA ratio remained above the endogenous levels at 8-hr postinfusion despite the fact that urinary ethanol was no longer measurable (<0.01 g/liter) after 5 to 6 hr.


CONCLUSIONS
Measuring the concentrations of methanol and the ratio of serotonin metabolites (5HTOL/5HIAA) in urine is a more sensitive way to monitor recent drinking, compared with analysis of ethanol in body fluids. Moreover, the concentration-time profiles of methanol and the 5HTOL/5HIAA ratio showed a good test-retest stability. The present intravenous infusion experiment confirms previous work on these markers when ethanol was given perorally. The urinary methanol and the 5HTOL/5HIAA ratio have applications in forensic and clinical medicine as indicators of acute alcohol consumption.
Jones
A W
AW
Department of Forensic Toxicology, University Hospital, Linköping, Sweden. wayne.jones@rmv.se
Helander
A
A
D000328:Adult; D015415:Biomarkers / Q000652:urine; D002492:Central Nervous System Depressants / Q000494:pharmacology / Q000652:urine*; D000431:Ethanol / Q000494:pharmacology / Q000652:urine*; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine*; D008297:Male; D000432:Methanol / Q000652:urine*; D015203:Reproducibility of Results; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D015415:Biomarkers; D002492:Central Nervous System Depressants; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D000432:Methanol