In most studies, the alcohol marker phosphatidylethanol (PEth) was used to differentiate social drinking from alcohol abuse. This study investigates PEth's potential in abstinence monitoring by performing a drinking study to assess the detection window of PEth after ingesting a defined amount of alcohol. After 2 weeks of abstinence, 16 volunteers ingested a single dose of alcohol, leading to an estimated blood alcohol concentration (BAC) of 1 g/kg. In the week after drinking, blood and urine samples were taken daily; in the second week, samples were taken every other day. PEth 16:0/18:1 and 16:0/18:2 were analyzed in blood by online-SPE-LC-MS/MS. Ethyl glucuronide and ethyl sulfate were determined in urine for abstinence monitoring. Prior to start of drinking, PEth 16:0/18:1 exceeded 30 ng/mL in blood samples of five volunteers despite the requested abstinence period. Positive PEth values resulted from drinking events prior to this abstinence period. After the start of drinking, maximum BACs were reached after 2 h with a mean of 0.80 ± 0.13 g/kg (range: 0.61-1.11 g/kg). PEth 16:0/18:1 increased within 8 h to maximum concentrations (mean: 88.8 ± 47.0 ng/mL, range: 37.2-208 ng/mL). After this event, PEth was detectable for 3 to 12 days with a mean half-life time of approximately 3 days. PEth has a potential in abstinence monitoring, since PEth could be detected for up to 12 days after a single drinking event. Further investigations are necessary, to establish cut-off levels for PEth as diagnostic marker for the determination of drinking habits like abstinence, social drinking, or risky alcohol consumption.

Phosphatidylethanol (PEth) is a new, highly specific alcohol marker. The aim of this study was to assess its diagnostic value in the liver transplant setting. In 51 pre- and 61 post-transplant patients with underlying alcoholic liver disease PEth, ethanol, methanol, carbohydrate-deficient transferrin (CDT), and ethyl glucuronide in urine (uEtG) and hair (hEtG) were tested and compared with patients' questionnaire reports. Twenty-eight (25%) patients tested positive for at least one alcohol marker. PEth alone revealed alcohol consumption in 18% of patients. With respect to detection of alcohol intake in the preceding week, PEth showed a 100% sensitivity. PEth testing was more sensitive than the determination of ethanol, methanol, CDT or uEtG alone [sensitivity 25% (confidence interval (CI) 95%, 7-52%), 25% (7-52%), 21% (6-45%) and 71% (41-91%), respectively], or ethanol, methanol and uEtG taken in combination with 73% (45-92%). Specificity of all markers was 92% or higher. Additional testing of hEtG revealed alcohol consumption in seven patients, not being positive for any other marker. Phosphatidylethanol was a highly specific and sensitive marker for detection of recent alcohol consumption in pre- and post-transplant patients. The additional determination of hEtG was useful in disclosing alcohol consumption 3-6 months retrospectively.

In addition to monitoring problematic or harmful alcohol consumption, drinking experiments indicated the potential of phosphatidylethanols (PEth) in abstinence monitoring. To date, no profound evaluation of thresholds for the differentiation of abstinence from moderate drinking and for detection of excessive consumption based on PEth homologues exists. Investigations with a large group of healthy volunteers (n=300) were performed to establish PEth reference values reflecting different drinking habits. Blood samples were analyzed for PEth 16:0/18:1 and 16:0/18:2 by online-SPE-LC-MS/MS method. Results were compared to AUDIT-C questionnaires, to the amounts of alcohol consumed during the two-weeks prior to blood sampling, and were statistically evaluated. PEth concentrations were significantly correlated with self-reported alcohol consumption (r>0.69) and with AUDIT-C scores (r>0.65). 4.0% of 300 volunteers reported abstinence (AUDIT-C score: 0), no PEth was detectable in their blood. PEth 16:0/18:1 concentrations below the limit of detection of 10.0ng/mL match with abstinence and light drinking habits (≤10g pure alcohol/day). However, some volunteers classified as "excessive alcohol consumers" had negative PEth results. In the group of volunteers classified as "moderate drinkers" (AUDIT-C score: 1-3 (women) and 1-4 (men)), 95% of the test persons had PEth 16:0/18:1 ranging from not detected to 112ng/mL, and PEth 16:0/18:2 ranging from not detected to 67.0ng/mL. Combination of self-reported alcohol consumption and AUDIT-C score showed that negative PEth results match with abstinence or light drinking. Moderate alcohol consumption resulted in PEth 16:0/18:1 from 0 to 112ng/mL and for PEth 16:0/18:2 ranged from 0 to 67.0ng/mL. Higher PEth concentrations indicated excessive alcohol consumption.

For early diagnosis and therapy of alcohol-related disorders, alcohol biomarkers are highly valuable. Concerning specificity, indirect markers can be influenced by nonethanol-related factors, whereas direct markers are only formed after ethanol consumption. Sensitivity of the direct markers depends on cut-offs of analytical methods, material for analysis and plays an important role for their utilization in different fields of application. Until recently, the biomarker phosphatidylethanol has been used to differentiate between social drinking and alcohol abuse. After method optimization, the detection limit could be lowered and phosphatidylethanol became sensitive enough to even detect the consumption of low amounts of alcohol. This perspective gives a summary of most common alcohol biomarkers and summarizes new developments for monitoring alcohol consumption habits.

Phosphatidylethanol (PEth) is considered as specific biomarker of alcohol consumption. Due to accumulation after repeated drinking, PEth is suitable to monitor long-term drinking behavior. To examine the applicability of PEth in "driving under the influence of alcohol" cases, 142 blood samples with blood alcohol concentrations (BAC) ranging from 0.0-3.12‰ were analyzed for the presence of PEth homologues 16:0/18:1 (889 ± 878 ng/mL; range