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André C, Sauton P, Dreinaza M, Diouf M, Bodeau S, Martinetti M, Trouillet R, de Groote C, Nandrino J, Alexandre A, Benzerouk F, Gierski F, Perney P, Grellet L, André J, Naassila M. Effect of the MyDéfi Smartphone Application on Binge Drinking Among University Students: Protocol of a Double-Blind Multicenter Prospective National Randomized Controlled Trial Using Phosphatidylethanol as a Biomarker-The SMARTBINGE Trial. Int J Methods Psychiatr Res 2025; 34:e70014. [PMID: 40165584 PMCID: PMC11959157 DOI: 10.1002/mpr.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 03/14/2025] [Accepted: 03/19/2025] [Indexed: 04/02/2025] Open
Abstract
OBJECTIVE The purpose of this paper is to describe a study protocol of a clinical trial exploring the effectiveness of the new mobile application MyDéfi proposing personalized feedback, on both alcohol consumption and quality of life, as well as the blood alcohol exposure biomarker phosphatidylethanol, in university students displaying binge drinking behavior. METHODS This prospective national multicentric randomized, two-arm (1:1), double-blind controlled trial will recruit 628 students (aged 18-25 years) with binge drinking behavior. Participants will be randomized in the "intervention" group (personalized feedback) or the "control" group (generic feedback) and will undergo four monthly visits. Monthly dried blood spot sample for measuring phosphatidylethanol concentration and online questionnaires will be collected. Our primary objective is to assess the reduction weekly standard drinks, through self-report gathered via MyDéfi. Secondary objectives will evaluate the application's impact on the dosage of phosphatidylethanol blood concentration and on quality of life". RESULTS Recruitment started in March 2024 and will end in March 2026. CONCLUSION This study aims to determine the effectiveness of two versions of the same mobile application (generic vs. personalized feedback) on alcohol consumption in students displaying binge drinking behavior. The effectiveness of the application will be measured, with a secondary objective of quantifying phosphatidylethanol. Our study will open new perspectives on the use of digital interventions for students who do not actively seek treatment. TRIAL REGISTRATION Trial registration number (NCT06084832), the date of registration (10th October 2023) and when this was done (16th October 2023). https://clinicaltrials.gov/study/NCT06084832.
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Affiliation(s)
- Camille André
- Groupe de Recherche sur l’Alcool & les PharmacodépendancesINSERM UMR 1247Université de Picardie Jules VerneAmiensFrance
| | - Pierre Sauton
- Groupe de Recherche sur l’Alcool & les PharmacodépendancesINSERM UMR 1247Université de Picardie Jules VerneAmiensFrance
| | - Méléna Dreinaza
- Groupe de Recherche sur l’Alcool & les PharmacodépendancesINSERM UMR 1247Université de Picardie Jules VerneAmiensFrance
| | - Momar Diouf
- Department of StatisticsAmiens Hospital UniversityAmiensFrance
| | - Sandra Bodeau
- Department of Clinical PharmacologyAmiens University Medical CenterAmiensFrance
| | - Margaret Martinetti
- Groupe de Recherche sur l’Alcool & les PharmacodépendancesINSERM UMR 1247Université de Picardie Jules VerneAmiensFrance
| | | | - Clara de Groote
- Laboratory SCALabUMR CNRS 9193University of LilleVilleneuve d'AscqFrance
| | | | - Adèle Alexandre
- Cognition Health Society Laboratory (C2S ‐ EA 6291)University of Reims Champagne ArdenneReimsFrance
| | - Farid Benzerouk
- Cognition Health Society Laboratory (C2S ‐ EA 6291)University of Reims Champagne ArdenneReimsFrance
| | - Fabien Gierski
- Cognition Health Society Laboratory (C2S ‐ EA 6291)University of Reims Champagne ArdenneReimsFrance
| | - Pascal Perney
- Addictions DepartmentCHU CaremeauUniversity of MontpellierMontpellierFrance
| | | | - Judith André
- Groupe de Recherche sur l’Alcool & les PharmacodépendancesINSERM UMR 1247Université de Picardie Jules VerneAmiensFrance
| | - Mickael Naassila
- Groupe de Recherche sur l’Alcool & les PharmacodépendancesINSERM UMR 1247Université de Picardie Jules VerneAmiensFrance
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Gomonit MM, Roman M, Skillman BN, Truver MT, Kronstrand R. Quantification of phosphatidylethanol 16:0/18:1 in blood using supercritical fluid chromatography-tandem mass spectrometry. J Anal Toxicol 2025; 49:289-298. [PMID: 40085069 DOI: 10.1093/jat/bkaf007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 02/01/2025] [Accepted: 03/13/2025] [Indexed: 03/16/2025] Open
Abstract
Phosphatidylethanol (PEth) consists of phospholipids synthesized in erythrocyte cell membranes in the presence of ethanol and serves as a sensitive and specific indicator of alcohol consumption. Further research on PEth formation, degradation, and stability in postmortem (PM) samples would support its routine application in forensic toxicology. A supercritical fluid chromatography-tandem mass spectrometry (SFC-MS-MS) method was developed and validated to quantify PEth 16:0/18:1 in blood. PEth 16:0/18:1 was extracted from blood (0.25 g) using an 8:2 (v/v) heptane:2-propanol mixture. Method validation results met American National Standards Institute/Academy Standards Board 036 guidelines. Recovery was >48%, and matrix effects were <20%. The linear range was 10-2500 ng/g, and lower limit of quantification was 10 ng/g. Bias was ±17.7%, and precision was <17.1% for all quality control levels. Carryover, endogenous, and exogenous interferences were negligible. Extracts were stable beyond 72 hours. In a proof-of-concept study reanalyzing 35 PM case samples, PEth concentrations ranged between 32.6 to 2476 ng/g. Short-term stability studies showed that fortified bovine blood (200 ng/g) preserved with 0.4% sodium fluoride (NaF) stored at room temperature had a 6.6% concentration drop after 48 hours, while blood stored at 4°C decreased by 13.5% over 14 days. Additionally, human PEth-positive blood preserved with 0.4% NaF showed a 6.7% decrease in in vivo PEth concentrations compared to a 17.5% decrease in heparin-preserved blood after 14 days at 4°C, supporting the use of 0.4% NaF in reducing PEth degradation over time. An in vitro model was also developed to simulate early PM PEth changes. Results found that PEth formation occurred in an ethanol concentration-dependent manner with minimal degradation, and considerations should be taken when interpreting PEth concentrations in cases with long PM interval, and if the decedent had a high blood alcohol concentration level and was left at elevated temperatures. This is the first SFC-MS-MS method successfully developed and validated for the analysis of PEth in PM samples.
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Affiliation(s)
- Munchelou M Gomonit
- Department of Forensic Science, College of Criminal Justice, Sam Houston State University, Huntsville, TX 77340, United States
| | - Markus Roman
- Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping 587 58, Sweden
| | - Britni N Skillman
- Department of Forensic Science, College of Criminal Justice, Sam Houston State University, Huntsville, TX 77340, United States
| | - Michael T Truver
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Robert Kronstrand
- Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping 587 58, Sweden
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Hose J, Juebner M, Thevis M, Andresen-Streichert H. Assessment and cross-validation of calibration transferability between dried blood spot sampling devices for accurate quantification of phosphatidylethanol. Anal Bioanal Chem 2025:10.1007/s00216-025-05897-x. [PMID: 40372410 DOI: 10.1007/s00216-025-05897-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 04/20/2025] [Accepted: 04/23/2025] [Indexed: 05/16/2025]
Abstract
Phosphatidylethanol (PEth) is a direct alcohol biomarker which is used in a variety of clinical and forensic contexts. Due to its limited stability in whole blood, PEth is routinely analysed using dried blood spots (DBS). There are many different commercially available sampling systems for DBS, but data on their comparability is scarce. The aim of this study was to develop and validate a LC-MS/MS method for the quantification of PEth 16:0/18:1 and PEth 16:0/18:2 for three different DBS sampling systems: Whatman™ filter paper (903 Protein Saver Cards), Mitra® and Capitainer®B Vanadate. The transferability of calibration curves and their applicability across these devices should be assessed. The results showed that DBS of all devices could be prepared and analysed using the same procedure. Validation was successful for the devices. The accuracy of QCs was best if quantified using the matching DBS sampling device calibration curve (bias < 15 %). Higher, but still acceptable, bias values were observed when using a Whatman™ calibration curve to quantify PEth in DBS of the Capitainer®B Vanadate system and vice versa. Mitra® QCs should only be quantified using device-specific calibration curves, as in all other cases, accuracy exceeded the limit of 15 %. We recommend analysing samples using device-specific calibrations at all times, as determined PEth concentrations might be crucial for patients and should not be subjected to any avoidable uncertainty.
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Affiliation(s)
- J Hose
- Department of Toxicology, Institute of Legal Medicine, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany.
| | - M Juebner
- Department of Toxicology, Institute of Legal Medicine, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany
| | - M Thevis
- Centre for Preventive Doping Research/Institute of Biochemistry, German Sport University Cologne, Cologne, Germany
| | - H Andresen-Streichert
- Department of Toxicology, Institute of Legal Medicine, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany
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Ververi C, Massano M, Alladio E, Salomone A, Vincenti M. Determination by UHPLC-QTOF-HRMS of Phosphatidylethanol (PEth) in Dried Blood Spots: Method Validation and Practical Application of a Rising Alcohol Abuse Biomarker With Minimally Invasive Sampling. Biomed Chromatogr 2025; 39:e70081. [PMID: 40211930 PMCID: PMC11986801 DOI: 10.1002/bmc.70081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 03/04/2025] [Accepted: 03/31/2025] [Indexed: 04/13/2025]
Abstract
The goal of our study was to develop and validate a simple, quick, and sensitive method to detect phosphatidylethanol (PEth) in dried blood spots (DBS). A 30-μL aliquot of blood was collected on a DBS card and allowed to dry at room temperature. Then, the spot was cut and transferred into a clean tube where the internal standard (PEth-D5) and 1-mL hexane were added followed by stirring, sonication, and centrifugation at room temperature. The dried supernatant was reconstituted with 30-μL acetonitrile and analyzed by UHPLC-HRMS-QTOF. Calibration curve was created at 20, 50, 100, 200, 300, and 500 ng/mL; the limit of detection was calculated at 5 ng/mL (S/N > 3) while accuracy, precision, recovery, and matrix effect were successfully evaluated, along with the analyte stability at different time intervals and temperatures. The study demonstrates that quantifying PEth 16:0/18:1 from DBS cards is feasible using UHPLC-QTOF or UHPLC-QqQ instrumentation while the QTOF method was validated and proved reliable for PEth detection to assess both excessive alcohol consumption and alcohol abstinence, matching current guidelines. Preliminary data on authentic samples confirmed the method's performance in terms of ease, sustainability, and speed, supporting its great potential for routine toxicological diagnosis of chronic alcohol abuse.
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Affiliation(s)
- Christina Ververi
- Department of ChemistryUniversity of TurinTurinItaly
- Centro Regionale AntidopingOrbassanoTOItaly
| | - Marta Massano
- Department of ChemistryUniversity of TurinTurinItaly
- Centro Regionale AntidopingOrbassanoTOItaly
| | - Eugenio Alladio
- Department of ChemistryUniversity of TurinTurinItaly
- Centro Regionale AntidopingOrbassanoTOItaly
| | - Alberto Salomone
- Department of ChemistryUniversity of TurinTurinItaly
- Centro Regionale AntidopingOrbassanoTOItaly
| | - Marco Vincenti
- Department of ChemistryUniversity of TurinTurinItaly
- Centro Regionale AntidopingOrbassanoTOItaly
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Andreassen TN, Gule M, Havnen H, Spigset O, Skråstad RB. A validated method for capillary phosphatidylethanol 16:0/18:1 quantification with two different 10-µl volumetric absorptive microsample devices in the same setup. J Anal Toxicol 2025; 49:231-240. [PMID: 39882943 DOI: 10.1093/jat/bkaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 01/16/2025] [Accepted: 01/28/2025] [Indexed: 01/31/2025] Open
Abstract
There is a growing interest for quantification of drugs in capillary blood. Phosphatidylethanol (PEth) is a biomarker for alcohol intake measured in whole blood, thus making it a candidate for capillary sampling. Our laboratory has been running a method for PEth quantification in venous blood since 2016, and we aimed to expand this method to also include capillary dried blood spot (DBS) samples. Two 10-µl volumetric absorptive microsampling (VAMS) devices, Capitainer®B Vanadate and Mitra®, were included in the method development and validated. Calibrators and quality controls were spiked during automatic sample extraction without the VAMS devices present, making it possible to extract and analyze both types of VAMS samples in the same setup. With the Mitra device, all pre-established validation criteria were fulfilled in the measuring range of 0.03 to 4.0 µM (21-2812 ng/mL), including method comparison with our venous blood method. Capitainer fulfilled all validation criteria, except for the accuracy of samples with PEth levels ≥ 0.5 µM (≥ 352 ng/mL) (deviation -17.1% to -20.5%). The correlation analysis between Capitainer and the venous blood results showed no constant bias, but an acceptable small proportional mean difference of -7.6%. Overall, the method validation results for both Capitainer and Mitra were considered acceptable. Both devices were found to be suitable for the analyses of PEth.
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Affiliation(s)
- Trine N Andreassen
- Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim 7006, Norway
| | - Marina Gule
- Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim 7006, Norway
| | - Hilde Havnen
- Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim 7006, Norway
| | - Olav Spigset
- Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim 7006, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7030, Norway
| | - Ragnhild Bergene Skråstad
- Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim 7006, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7030, Norway
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Jørgenrud B, McQuade T, Maria MH, Nilsson G, Berg T. Buffer-free high pH mobile phase LC-MS/MS for determination of the alcohol biomarker phosphatidylethanol 16:0/18:1 and 20 drugs and metabolites in whole blood. Talanta 2025; 282:126964. [PMID: 39366246 DOI: 10.1016/j.talanta.2024.126964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/10/2024] [Accepted: 09/25/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND Acidic mobile phases are commonly used in reversed phase liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalysis. However, increased sensitivity, improved peak symmetry, and increased retention, especially for basic hydrophilic drugs have been observed using basic mobile phases. In our previous acidic mobile phase LC-MS/MS method we needed two injections (0.4 and 2.0 μL) of each sample for this task, which is inefficient. The aim of this study was to investigate if basic mobile phase LC-MS/MS could be used to determine phosphatidylethanol 16:0/18:1 and 20 other drugs and metabolites with satisfactory sensitivity in one single run. METHODS Whole blood was prepared by 96-well supported-liquid extraction using heptane/ethyl acetate/2-propanol (16:64:20, v:v:v). Chromatographic separation was achieved on an Acquity BEH C18 column (50 × 2.1 mm I.D.), using a mobile phase with 0.025 % ammonia, pH 10.7 (Solvent A) and methanol (Solvent B). All compounds had isotope-labelled internal standards. RESULTS The method was fully validated. Recovery was between 63 and 91 % for 20 compounds and 10 % for benzoylecgonine. Matrix effects were low, except for ion enhancement of buprenorphine and ion suppression for THC. However, internal standards compensated for these effects. Inter-assay precision and accuracy were < ± 20 % for all compounds at five tested concentrations, except for methamphetamine at the highest concentration. CONCLUSION An LC-MS/MS method for simultaneous determination of PEth 16:0/18:1 and 20 drugs and metabolites in whole blood were for the first time developed and validated. Retention of PEth 16:0/18:1 was, in contrast to the other 20 compounds, largely affected by mobile phase buffer concentration. The buffer free basic mobile phase ensured that phosphatidylethanol 16:0/18:1 eluted before most of the unwanted phospholipids.
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Affiliation(s)
- Benedicte Jørgenrud
- Section of Forensic Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway.
| | - Tao McQuade
- Section of Forensic Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway
| | - Marisa H Maria
- Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749 -016, Lisboa, Portugal
| | - Galina Nilsson
- Section of Forensic Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway
| | - Thomas Berg
- Section of Forensic Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, N-0424, Oslo, Norway.
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Häkkinen M, Arponen A, Jylhä A, Sulin K, Gunnar T. Phosphatidylethanol is a promising tool for screening alcohol consumption during pregnancy. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:1892-1897. [PMID: 39147721 DOI: 10.1111/acer.15418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/15/2024] [Accepted: 07/19/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND Prenatal alcohol exposure (PAE) is one of the leading causes of preventable developmental disabilities. A lack of objective screening methods results in an under-recognition of the phenomenon. Phosphatidylethanol (PEth) is a specific ethanol biomarker that reveals alcohol intake up to several weeks after alcohol use. So far, PEth has mostly been a tool for detecting moderate and heavy drinking. With lower PEth cut-offs, revealing even minor prenatal alcohol consumption is possible. We aimed to find out if a sensitive method for PEth analysis would give additional information about PAE and to assess the cut-off value for a positive alcohol result in prenatal screening. METHODS The study was an observational study of 3000 anonymous blood samples collected from the Helsinki University Hospital Diagnostic Center between June and September 2023. The Finnish Red Cross Blood Service received the samples originally for blood group typing and antibody screening as part of the prenatal blood screening program. We developed a sensitive PEth 16:0/18:1 analysis method using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) equipment after liquid-liquid extraction of PEth from whole blood. The lower limit of quantification was 1 ng/mL. RESULTS PEth was ≥2 ng/mL in 5.2% of the cases, ≥8 ng/mL in 2.0%, and ≥20 ng/mL in 1.0%. The detection time of PEth can be several weeks, especially with low PEth concentrations and after heavy alcohol consumption. It remained unknown whether the positive PEth tests resulted from drinking deliberately during pregnancy or before pregnancy recognition. CONCLUSIONS We suggest adding PEth 16:0/18:1 to a routine prenatal blood screening program with a cut-off of 2 ng/mL-and in positive cases, clinical evaluation and retesting in 2-4 weeks. In clinical settings, information on gestational week and alcohol consumption before pregnancy is relevant and needs to be considered when interpreting low PEth concentrations.
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Affiliation(s)
- Margareeta Häkkinen
- Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland
- Department of Psychiatry, University of Helsinki, Helsinki, Finland
- Addiction Hospital, A-Clinic Ltd, Järvenpää, Finland
| | - Anne Arponen
- Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Antti Jylhä
- Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Kati Sulin
- Finnish Red Cross Blood Service, Vantaa, Finland
| | - Teemu Gunnar
- Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland
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Smith CC, Stevens J, Novelli M, Maskey D, Sutherland GT. Phosphatidylethanol in post-mortem brain: Correlation with blood alcohol concentration and alcohol use disorder. Alcohol 2024; 119:17-22. [PMID: 38763230 DOI: 10.1016/j.alcohol.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/15/2024] [Accepted: 05/15/2024] [Indexed: 05/21/2024]
Abstract
Phosphatidylethanol (PEth) is an alcohol derivative that has been employed as a blood-based biomarker for regular alcohol use. This study investigates the utility of phosphatidylethanol (PEth) as a biomarker for assessing alcohol consumption in post-mortem brain tissue. Using samples from the New South Wales Brain Tissue Resource Centre, we analysed PEth(16:0/18:1) levels in the cerebellum and meninges of individuals with varying histories of alcohol use, including those diagnosed with alcohol use disorder (AUD) and controls. Our findings demonstrate a significant correlation between PEth levels and blood alcohol content (BAC) at the time of death, supporting the biomarker's sensitivity to recent alcohol intake. Furthermore, this study explores the potential of PEth levels in differentiating AUD cases from controls, taking into consideration the complexities of diagnosing AUD post-mortem. The study also examined the relationship between PEth levels and liver pathology, identifying a link with the severity of liver damage. These results underscore the value of PEth as a reliable indicator of alcohol consumption and its potential contributions to post-mortem diagnostics and consequently, research into alcohol-related brain damage.
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Affiliation(s)
- Caine C Smith
- New South Wales Brain Tissue Research Centre, Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
| | - Julia Stevens
- New South Wales Brain Tissue Research Centre, Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
| | - Mario Novelli
- New South Wales Brain Tissue Research Centre, Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
| | - Dhiraj Maskey
- New South Wales Brain Tissue Research Centre, Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
| | - Greg T Sutherland
- New South Wales Brain Tissue Research Centre, Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.
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de Bejczy A. Phosphatidylethanol (B-PEth) and other direct and indirect biomarkers of alcohol consumption. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2024; 175:313-344. [PMID: 38555120 DOI: 10.1016/bs.irn.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
When identifying, preventing and treating alcohol use disorder, a correct estimation of alcohol intake is essential. An objective marker is preferred as self-reported alcohol intake suffers from bias, and the use of alcohol biomarkers is increasing globally. An easy-to-use blood biomarker to correctly assess alcohol consumption is an invaluable asset in alcohol treatment strategies, as well as in alcohol research studies. The specific, cumulative, biomarker phosphatidylethanol, mirroring the past two weeks of consumption, has shown superiority over traditional biomarkers and is an attractive choice of proxy for alcohol intake.
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Affiliation(s)
- Andrea de Bejczy
- Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Addiction and Dependency, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Cameron CM, Vuong K, McWhinney B, Zournazi A, Manzanero S, Warren J, Mitchell G, Vallmuur K, Howell T, Ungerer JPJ. Factors associated with higher alcohol concentrations in emergency department presentations: PACE study. Drug Alcohol Rev 2023; 42:1796-1806. [PMID: 37703216 DOI: 10.1111/dar.13744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 07/10/2023] [Accepted: 08/14/2023] [Indexed: 09/15/2023]
Abstract
INTRODUCTION The health impact from alcohol is of recognised concern, from acute intoxication as well as increased risk of chronic health issues over time. Identifying factors associated with higher alcohol consumption when presenting to the emergency department (ED) will inform public health policy and enable more targeted health care and appropriate referrals. METHODS Secondary testing of blood samples collected during routine clinical care of 1160 ED patients presenting to the Royal Brisbane and Women's Hospital in Queensland, Australia, for 10 days between 22 January and 1 February 2021. Alcohol was measured by blood ethanol (intake in recent hours) and phosphatidylethanol (PEth; intake over 2-4 weeks). Zero-inflated negative binomial regression was used to identify demographic and clinical factors associated with higher alcohol concentrations. RESULTS Males were found to have 83% higher blood ethanol and 32% higher PEth concentrations than females (adjusted rate ratio [ARR] 1.83, 95% confidence interval [CI] 1.37-2.45 and ARR 1.32, 95% CI 1.04-1.68, respectively). Blood ethanol concentrations were 3.4 times higher for those 18-44 years, compared to those aged 65+ (ARR 3.40, 95% CI 2.40-4.82) whereas PEth concentrations were found to be the highest in those aged 45-64 years, being 70% higher than those aged 65+ (ARR 1.70, 95% CI 1.19-2.44). Patients brought in involuntarily had eight-times higher blood ethanol concentrations than those who self-attended. DISCUSSION AND CONCLUSIONS This study used two alcohol markers to identify factors associated with higher alcohol concentrations in emergency presentations. The findings demonstrate how these biomarkers can provide informative data for public health responses and monitoring of alcohol use trends.
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Affiliation(s)
- Cate M Cameron
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia
- Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | - Kim Vuong
- Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | - Brett McWhinney
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Anna Zournazi
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Silvia Manzanero
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia
- School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia
| | - Jacelle Warren
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia
- Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | - Gary Mitchell
- Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia
- School of Medicine, University of Queensland, Brisbane, Australia
| | - Kirsten Vallmuur
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia
- Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | | | - Jacobus P J Ungerer
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane and Women's Hospital, Brisbane, Australia
- Faculty of Biomedical Science, University of Queensland, Brisbane, Australia
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Maria M, Neng NR, Berg T. An accurate and precise liquid chromatography-tandem mass spectrometry method for the determination of six phosphatidylethanol homologues in whole blood with phospholipid interferences minimized. J Chromatogr A 2023; 1711:464451. [PMID: 39491082 DOI: 10.1016/j.chroma.2023.464451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/26/2023] [Accepted: 10/12/2023] [Indexed: 11/05/2024]
Abstract
Alcohol consumption is associated with a wide risk of different diseases, injury and death, and has significant social and economic consequences worldwide. Phosphatidylethanol (PEth) is a group of promising direct alcohol biomarkers, with a significantly longer half-life in blood than ethanol, which can be measured to predict different drinking patterns, such as heavy- and social drinking. This study aimed to develop and validate an accurate and precise LC-MS/MS method for the determination of six PEth homologues in whole blood with minimal interference from unwanted phospholipids. Different organic solvent mixtures for liquid-liquid extraction were investigated to obtain satisfactory recovery of PEth homologues and removal of the lyso-phospholipids and other early eluting phospholipids. The mixture of heptane/2-propanol (80:20, v:v) gave lower phospholipid background and better signal/noise values for the PEth peaks. An LC-MS/MS TQ-S system from Waters was used for the instrumental analysis. The main part of unwanted phospholipids were separated from the PEth homologues on an Acquity BEH C18 column (50 × 2.1 mm ID, 1.7 µm particles) using a buffer-free mobile phase of 0.025 % ammonia in Type 1 water, pH 10.7, as solvent A and methanol as solvent B. Validation and quantification of 22 authentic blood samples showed that the developed LC-MS/MS method is sensitive, precise and accurate for the determination of the six PEth homologues in whole blood. Lower limit of quantification was 10 nM for all compounds. No matrix effects were observed, possibly due to the successful strategies incorporated to avoid the influence of unwanted phospholipids.
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Affiliation(s)
- Marisa Maria
- Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749 -016 Lisboa, Portugal
| | - Nuno R Neng
- Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749 -016 Lisboa, Portugal; Laboratório de Ciências Forenses e Psicológicas Egas Moniz, Molecular Pathology and Forensic Biochemistry Laboratory, Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz School of Health and Science, Campus Universitário, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal
| | - Thomas Berg
- Section of Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, P.O. Box 4950 Nydalen, N-0424 Oslo, Norway.
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12
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Perilli M, Toselli F, Franceschetto L, Cinquetti A, Ceretta A, Cecchetto G, Viel G. Phosphatidylethanol (PEth) in Blood as a Marker of Unhealthy Alcohol Use: A Systematic Review with Novel Molecular Insights. Int J Mol Sci 2023; 24:12175. [PMID: 37569551 PMCID: PMC10418704 DOI: 10.3390/ijms241512175] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of unhealthy alcohol use. This systematic review aims to investigate the molecular characteristics of PEth and summarize the last ten years of published literature and its use compared to structured questionnaires. A systematic search was performed, adhering to PRISMA guidelines, through "MeSH" and "free-text" protocols in the databases PubMed, SCOPUS, and Web of Science. The inclusion criteria were as follows: PEth was used for detecting unhealthy alcohol consumption in the general population and quantified in blood through liquid chromatography coupled to mass spectrometry, with full texts in the English language. Quality assessment was performed using the JBI critical appraisal checklist. Twelve papers were included (0.79% of total retrieved records), comprising nine cross-sectional studies and three cohort studies. All studies stratified alcohol exposure and quantified PEth 16:0/18:1 through liquid chromatography coupled to mass spectrometry (LC-MS) in liquid blood or dried blood spots (DBS) with lower limits of quantitation (LLOQ) ranging from 1.7 ng/mL to 20 ng/mL. A correlation between blood PEth level and the amount of alcohol ingested in the previous two weeks was generally observed. PEth interpretative cut-offs varied greatly among the included records, ranging from 4.2 ng/mL to 250 ng/mL, with sensitivity and specificity in the ranges of 58-100% and 64-100%, respectively. Although the biomarker seems promising, further research elucidating the variability in PEth formation and degradation, as well as the molecular mechanisms behind that variability, are necessary.
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Affiliation(s)
| | | | | | | | | | | | - Guido Viel
- Legal Medicine and Toxicology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via G. Falloppio 50, 35121 Padova, Italy; (M.P.); (F.T.); (L.F.); (A.C.); (A.C.); (G.C.)
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13
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Reisfield GM, Teitelbaum SA, Jones JT, Mason D, Bleiweis M, Lewis B. Blood Phosphatidylethanol (PEth) Concentrations following Intensive Use of an Alcohol-based Hand Sanitizer. J Anal Toxicol 2023; 46:979-990. [PMID: 34748012 DOI: 10.1093/jat/bkab115] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/28/2021] [Accepted: 11/05/2021] [Indexed: 01/26/2023] Open
Abstract
Alcohol use disorders are prevalent in the USA and throughout the world. Monitoring for alcohol abstinence is useful in several clinical and forensic contexts. The direct alcohol biomarkers have the requisite sensitivity and specificity for abstinence monitoring. The relatively new direct biomarker phosphatidylethanol (PEth), measured in blood, is gaining increasing acceptance in monitoring abstinence from beverage alcohol consumption, but there remains little research addressing the potential for PEth formation consequent to incidental alcohol exposures. In the midst of the coronavirus disease 2019 pandemic, high-alcohol content hand sanitizer is a particularly important source of nonbeverage alcohol exposure. To assess the extent of alcohol absorption and subsequent formation of blood PEth related to intensive use of high alcohol content hand sanitizer, we recruited 15 participants to use a 70% ethyl alcohol-based hand sanitizer 24-100 times daily, for 12-13 consecutive days. Blood was analyzed for PEth 16:0/18:1 by liquid chromatography--tandem mass spectrometry. Our hypothesis that blood PEth concentrations would fail to reach a 20 ng/mL threshold was confirmed. This work adds to the nascent literature on the effects of incidental alcohol exposures on blood PEth formation.
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Affiliation(s)
- Gary M Reisfield
- UF Health Springhill, University of Florida College of Medicine, 4037 NW 86th Terrace, Gainesville, FL 32606, USA
| | - Scott A Teitelbaum
- University of Florida College of Medicine, 1600 Sw Archer Road, Gainesville, FL 32610, USA
| | - Joseph T Jones
- United States Drug Testing Laboratories, Inc., 1700 S Mount Prospect Road, Des Plaines, IL 60018, USA
| | - Dana Mason
- University of Florida College of Medicine, 1600 Sw Archer Road, Gainesville, FL 32610, USA
| | - Max Bleiweis
- University of Florida College of Medicine, 1600 Sw Archer Road, Gainesville, FL 32610, USA
| | - Ben Lewis
- University of Florida College of Medicine, 1600 Sw Archer Road, Gainesville, FL 32610, USA
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14
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Stöth F, Kotzerke E, Thierauf-Emberger A, Weinmann W, Schuldis D. Can PEth be Detected with a Cutoff of 20 ng/mL after Single Alcohol Consumption? J Anal Toxicol 2023; 46:e232-e238. [PMID: 36107736 DOI: 10.1093/jat/bkac069] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 08/15/2022] [Accepted: 09/13/2022] [Indexed: 01/26/2023] Open
Abstract
Phosphatidylethanol (PEth) can be determined in capillary blood collected as dried blood spots (DBS) and is a promising direct alcohol biomarker for the determination of drinking habits. Its use for abstinence monitoring needs to be evaluated. Studies with patients undergoing alcohol withdrawal have shown that the elimination of PEth can take up to 2 months. For the determination of PEth 16:0/18:1, a cutoff of 20 ng/mL has been agreed upon in the major US laboratories. However, it is not yet clear what minimum blood alcohol concentrations (BACs) have to be achieved by a single drinking episode to result in PEth concentrations above this cutoff after previous long-term abstinence. To determine whether low drinking amounts can result in a positive PEth concentration above 20 ng/mL, we recruited 12 participants ('social' drinkers). After 4 weeks of abstinence, alcohol was consumed at two separate drinking events with target BACs of 0.5 and 0.3 g/kg, resulting in maximum BACs in the ranges of 0.30-0.63 g/kg and 0.10-0.28 g/kg, respectively. Capillary blood was collected at different time points of the drinking experiment, and PEth was extracted from DBS and analyzed by liquid chromatography-tandem mass spectrometry. Despite drinking doses up to 0.58 g ethanol per kg body weight and reaching BACs of up to 0.63 g/kg, PEth 16:0/18:1 and PEth 16:0/18:2 could not be detected at or above the 20 ng/mL cutoff in any participant at any time after the drinking events. We conclude that after long-term abstinence the cutoff of 20 ng/mL for single alcohol consumption leading to BACs up to 0.63 g/kg is not exceeded.
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Affiliation(s)
- Frederike Stöth
- Institute of Forensic Medicine, Forensic Toxicology and Chemistry, University of Bern, Murtenstrasse 26, 3008 Bern, Switzerland
| | - Ephraim Kotzerke
- Institute of Forensic Medicine, Medical Center, University of Freiburg, Albertstraße 9, 79104 Freiburg, Germany
| | - Annette Thierauf-Emberger
- Institute of Forensic Medicine, Medical Center, University of Freiburg, Albertstraße 9, 79104 Freiburg, Germany
| | - Wolfgang Weinmann
- Institute of Forensic Medicine, Forensic Toxicology and Chemistry, University of Bern, Murtenstrasse 26, 3008 Bern, Switzerland
| | - Dominik Schuldis
- Institute of Forensic Medicine, Medical Center, University of Freiburg, Albertstraße 9, 79104 Freiburg, Germany
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15
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Cameron CM, Vuong K, McWhinney B, Zournazi A, Manzanero S, Warren J, Mitchell G, McCreanor V, Vallmuur K, Howell T, Ungerer JPJ. Prevalence of alcohol consumption in emergency presentations: Novel approach using two biomarkers, ethanol and phosphatidylethanol. Drug Alcohol Rev 2023; 42:146-156. [PMID: 36054789 PMCID: PMC10087033 DOI: 10.1111/dar.13534] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 08/04/2022] [Accepted: 08/04/2022] [Indexed: 01/10/2023]
Abstract
INTRODUCTION The aim was to determine the prevalence of alcohol-related presentations to an emergency department (ED) in a major Australian hospital, through a novel surveillance approach using two biomarkers, blood ethanol and phosphatidylethanol (PEth). METHODS Observational study using secondary testing of blood samples collected during routine clinical care of ED patients presenting to the Royal Brisbane and Women's Hospital in Queensland, Australia, between 22 January and 2 February 2021. Data were collected from 1160 patients during the 10-day study period. The main outcomes were the prevalence of acute alcohol intake, as determined by blood ethanol, and recent use over 2-4 weeks, as determined by PEth concentrations, for all ED presentations and different diagnostic groups. RESULTS The overall prevalence for blood ethanol was 9.3% (95% confidence interval [CI] 7.8%, 11.1%), 5.3% for general medical presentations, increasing four-fold to 22.2% for injury presentations. The overall prevalence of PEth positive samples was 32.5% (95% CI 29.9%, 35.3%) and 41.4% for injury presentations. There were 263 (25.3%) cases that tested negative for acute blood ethanol but positive for PEth concentrations indicative of significant to heavy medium-term alcohol consumption. DISCUSSION AND CONCLUSIONS This novel surveillance approach demonstrates that using blood ethanol tests in isolation significantly underestimates the prevalence of medium-term alcohol consumption in ED presentations. Prevalence of alcohol use was higher for key diagnostic groups such as injury presentations. Performing periodic measurement of both acute and medium-term alcohol consumption accurately and objectively in ED presentations, would be valuable for informing targeted public health prevention and control strategies.
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Affiliation(s)
- Cate M Cameron
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia.,Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | - Kim Vuong
- Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | - Brett McWhinney
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia
| | - Anna Zournazi
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia
| | - Silvia Manzanero
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia.,School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia
| | - Jacelle Warren
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia.,Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | - Gary Mitchell
- Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia.,School of Medicine, University of Queensland, Brisbane, Australia
| | - Victoria McCreanor
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia.,Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | - Kirsten Vallmuur
- Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia.,Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia
| | | | - Jacobus P J Ungerer
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane and Women's Hospital, Metro North Health, Brisbane, Australia.,Faculty of Biomedical Science, University of Queensland, Brisbane, Australia
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16
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Determination of eight phosphatidylethanol homologues in blood by reversed phase liquid chromatography–tandem mass spectrometry – How to avoid co-elution of phosphatidylethanols and unwanted phospholipids. J Chromatogr A 2022; 1684:463566. [DOI: 10.1016/j.chroma.2022.463566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/11/2022] [Accepted: 10/12/2022] [Indexed: 11/23/2022]
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17
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Van Uytfanghe K, Heughebaert L, Abatih E, Stove CP. Set-up of a population-based model to verify alcohol abstinence via monitoring of the direct alcohol marker phosphatidylethanol 16:0/18:1. Addiction 2022; 117:2108-2118. [PMID: 35072319 DOI: 10.1111/add.15811] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 01/03/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Phosphatidylethanol 16:0/18:1 (PEth) is a biomarker for alcohol intake. It has a half-life of 7.9 days. Chronic alcohol consumption causes high PEth values. It can take weeks before PEth values fall below the decision limit for 'alcohol abstinence'. Our aim was to validate whether alcohol abstinence can be determined based on two consecutive PEth results above the decision limit. DESIGN Observational study. SETTING Belgium, February 2019. The study was linked to a social initiative in Belgium, 'Tournée Minérale'. PARTICIPANTS Adults (aged > 18 years, n = 796) with varying drinking habits who self-reportedly refrained from alcohol consumption during the study. MEASUREMENTS A validated liquid chromatography-tandem mass spectrometry method was used to quantify PEth in participants' dried blood samples, collected at three time-points via remote fingerprick-based self-sampling. FINDINGS A population-based algorithm to evaluate abstinence based on 95% prediction limits was developed by fitting a linear mixed-effect model to discern patterns in PEth elimination over time. It took intra- and inter-individual variability into consideration. The algorithm was included in a two-step decision tree, assessing whether (i) PEth values fell within the prediction interval and (ii) the slope between two PEth values was consistent with no alcohol consumption. Data for 74 participants reporting no alcohol intake during the study were used for validation. With a detection limit of 'four units spread over 14 days', the sensitivity and specificity of the decision tree was 89%. CONCLUSIONS Claims of alcohol abstinence can be verified using a two-step decision tree for phosphatidylethanol 16:0/18:1 values, even when those values are above the limit for 'alcohol abstinence'.
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Affiliation(s)
- Katleen Van Uytfanghe
- Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Liesl Heughebaert
- Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Emmanuel Abatih
- Fostering Innovative Research Based on Evidence (FIRE), Ghent University, Ghent, Belgium
| | - Christophe P Stove
- Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
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18
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Prevalence of and Risk Factors Associated with Alcohol Overconsumption at 2 Years After Bariatric Surgery. Obes Surg 2022; 32:1-6. [PMID: 35469080 PMCID: PMC9276548 DOI: 10.1007/s11695-022-06060-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 04/13/2022] [Accepted: 04/13/2022] [Indexed: 12/25/2022]
Abstract
Abstract
Introduction
Alcohol overconsumption remains one of the adverse effects associated with bariatric surgery. Many previous studies have used subjective methods to evaluate the prevalence of alcohol overconsumption. In 2018, Örebro University Hospital started to use phosphatidylethanol 16:0/18:1 (PEth) as a screening tool pre- and postbariatric surgery. Research exploring alcohol use after bariatric surgery assessed with PEth is scarce.
Aim
The aim of this study is to evaluate the prevalence of alcohol overconsumption in bariatric surgery patients measured 2 years postoperatively with PEth and to identify possible risk factors associated with alcohol overconsumption.
Methods
This was a register-based retrospective, observational cohort study with PEth results collected from medical records at Örebro University Hospital. Patients who underwent bariatric surgery between January 2016 and June 2019 and who were registered in the Scandinavian Obesity Surgery Registry (SOReg) were included.
Results
PEth results from 410 bariatric surgery patients were identified. PEth values significantly increased from baseline to the postoperative follow-up (from 3.0% before surgery to 8.3% at the 2-year follow-up). In a univariate logistic regression analysis, the associated risk factors were found to be male sex (odds ratio, OR 2.14), older age (OR 1.06), and hypertension (OR 3.32).
Conclusion
The prevalence of alcohol overconsumption measured with PEth 2 years after bariatric surgery was 8.3% and was associated with male sex, older age, and hypertension. More studies are needed to validate the results of this study because it is not known whether PEth values are affected by bariatric surgery.
Graphical abstract
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19
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Selim R, Zhou Y, Rupp LB, Trudeau S, Naffouj S, AlShamaa O, Ahmed A, Jafri SM, Gordon SC, Segal A, Gonzalez HC. Availability of PEth testing is associated with reduced eligibility for liver transplant among patients with alcohol-related liver disease. Clin Transplant 2022; 36:e14595. [PMID: 35041223 DOI: 10.1111/ctr.14595] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 12/20/2021] [Accepted: 01/04/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings. METHODS Medical record data were collected for patients who initiated transplant evaluation due to alcohol-related liver disease in the pre-PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine-Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use. RESULTS 375 patients with alcohol-related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW-adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (p<0.05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol-related termination/delisting than those in the pre-PEth era (sHR = 2.86; 95%CI 1.67-4.97) CONCLUSION: We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol-related liver disease. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Ranya Selim
- Department of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI
| | - Yueren Zhou
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI
| | - Loralee B Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI
| | - Sheri Trudeau
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI
| | - Sandra Naffouj
- Department of Internal Medicine, Henry Ford Health System, Detroit, MI
| | - Omar AlShamaa
- Department of Internal Medicine, Henry Ford Health System, Detroit, MI
| | | | - Syed-Mohammed Jafri
- Department of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI.,Wayne State University School of Medicine, Detroit, MI
| | - Stuart C Gordon
- Department of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI.,Wayne State University School of Medicine, Detroit, MI
| | - Antu Segal
- Wayne State University School of Medicine, Detroit, MI.,Transplant Institute, Henry Ford Health System, Detroit, MI
| | - Humberto C Gonzalez
- Department of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI.,Wayne State University School of Medicine, Detroit, MI
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20
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DiBattista A, Ogrel S, MacKenzie AE, Chakraborty P. Quantitation of phosphatidylethanols in dried blood spots to determine rates of prenatal alcohol exposure in Ontario. Alcohol Clin Exp Res 2021; 46:243-251. [PMID: 34939205 DOI: 10.1111/acer.14766] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 11/04/2021] [Accepted: 12/17/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Estimating rates of prenatal alcohol exposure (PAE) in a population is necessary to ensure that proper medical and social supports and interventions are in place. This study sought to estimate PAE in Ontario, Canada by quantifying phosphatidylethanol (PEth) homologues in over 2000 residual neonatal dried blood spots (DBS). METHODS A random selection of 2011 residual DBS collected over a 1-week time period were anonymized and extracted. A targeted liquid chromatography-mass spectrometry method was used to quantify 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (PEth (16:0/18:1) or POPEth), the clinically accepted biomarker, and six additional PEth homologues. A POPEth level above the United States Drug Testing Laboratories (USDTL) cutoff up to 4 weeks predelivery was indicative of PAE. All PEth homologues were correlated to one another and logistic regression was used to determine the association between PAE status and infant characteristics. RESULTS The estimated rate of PAE in Ontario, up to the last 4 weeks of gestation, was 15.5% (POPEth >28.5 nM). Most PEth homologues were moderately to strongly correlated to one another. A low birth weight and preterm birth were both associated with PAE, while being small for gestational age had lower odds of PAE. CONCLUSIONS The results of this study suggest that PAE may be more prevalent in Ontario than previous estimates by self-report or meconium testing. These findings support the need to consider the effectiveness of current interventions and the design of new interventions to address this significant public health issue.
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Affiliation(s)
- Alicia DiBattista
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | - Svetlana Ogrel
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | - Alex E MacKenzie
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.,Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Pranesh Chakraborty
- Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.,Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
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21
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Vuong KA, Manzanero S, Ungerer JPJ, Mitchell G, McWhinney B, Vallmuur K, Warren J, McCreanor V, Howell T, Pollard C, Schuetz M, Zournazi A, Cameron CM. Prevalence of Alcohol Consumption in Emergency department presentations (PACE) in Queensland, Australia, using alcohol biomarkers ethanol and phosphatidylethanol: an observational study protocol. BMJ Open 2021; 11:e047887. [PMID: 34753753 PMCID: PMC8578965 DOI: 10.1136/bmjopen-2020-047887] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Alcohol use in patients presenting to the emergency department (ED) is a significant problem in many countries. There is a need for valid and reliable surveillance of the prevalence of alcohol use in patients presenting to the ED, to provide a more complete picture of the risk factors and inform targeted public health interventions. This PACE study will use two biomarkers, blood ethanol and phosphatidylethanol (PEth), to determine the patterns, presence and level of alcohol use in patients presenting to an Australian ED. METHODS AND ANALYSIS This is an observational prevalence study involving the secondary use of routinely collected blood samples from patients presenting to the Royal Brisbane and Women's Hospital (RBWH) Emergency and Trauma Centre (ETC). Samples will be tested for acute and medium-term alcohol intake using the two biomarkers blood ethanol and PEth respectively, over one collection period of 10-12 days. Descriptive statistics such as frequencies, percentages, means, SD, medians and IQRs, will be used to describe the prevalence, pattern and distribution of acute and medium-term alcohol intake in the study sample. The correlation between acute and medium-term alcohol intake levels will also be examined. ETHICS AND DISSEMINATION This study has been approved by the RBWH Human Research Ethics Committee (reference, LNR/2019/QRBW/56859). Findings will be disseminated to key stakeholders such as RBWH ETC, Australasian College for Emergency Medicine, Royal Australasian College of Surgeons, Statewide Clinical Networks, and used to inform clinicians and hospital services. Findings will be submitted for publication in peer-reviewed journals and presentation at appropriate conferences.
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Affiliation(s)
- Kim A Vuong
- Australian Centre for Health Services Innovation (AusHSI), Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Queensland, Australia
- Centre for Accident Research and Road Safety - Queensland (CARRS-Q), Queensland University of Technology, Brisbane, Queensland, Australia
| | - Silvia Manzanero
- Jamieson Trauma Institute, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
- School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Jacobus P J Ungerer
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
- Faculty of Biomedical Science, The University of Queensland, Brisbane, Queensland, Australia
| | - Gary Mitchell
- Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
- School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Brett McWhinney
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
| | - Kirsten Vallmuur
- Australian Centre for Health Services Innovation (AusHSI), Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Queensland, Australia
- Jamieson Trauma Institute, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
| | - Jacelle Warren
- Australian Centre for Health Services Innovation (AusHSI), Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Queensland, Australia
- Jamieson Trauma Institute, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
| | - Victoria McCreanor
- Australian Centre for Health Services Innovation (AusHSI), Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Queensland, Australia
- Jamieson Trauma Institute, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
| | | | - Clifford Pollard
- Jamieson Trauma Institute, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
| | - Michael Schuetz
- Jamieson Trauma Institute, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
- School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Anna Zournazi
- Chemical Pathology, Pathology Queensland, Queensland Health, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
| | - Cate M Cameron
- Australian Centre for Health Services Innovation (AusHSI), Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Queensland, Australia
- Jamieson Trauma Institute, Royal Brisbane & Women's Hospital (RBWH), Metro North Health, Brisbane, Queensland, Australia
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22
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Reisfield GM, Teitelbaum SA, Jones JT, Mason D, Bleiweis M, Lewis B. Blood Phosphatidylethanol Concentrations Following Regular Exposure to an Alcohol-Based Mouthwash. J Anal Toxicol 2021; 45:950-956. [PMID: 33024993 DOI: 10.1093/jat/bkaa147] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/04/2020] [Accepted: 10/02/2020] [Indexed: 02/06/2023] Open
Abstract
Direct biomarkers of ethanol are used to monitor individuals who are required to abstain from ethanol consumption. In recent years, blood phosphatidylethanol (PEth) has gained acceptance in clinical and forensic contexts as an abstinence marker. Its elimination half-life of several days provides a window of detection of days to weeks. However, there is no research addressing the extent of PEth formation related to extraneous ethanol exposures. To assess the degree of ethanol absorption and subsequent formation of blood PEth related a common extraneous exposure, regular use of an ethanol-containing mouthwash, we recruited 16 participants to gargle with an alcohol-based mouthwash (21.6% ethanol) 4 times daily, for 12 consecutive days. Blood was analyzed for PEth 16:0/18:1 by liquid chromatography-tandem mass spectrometry. Our hypothesis that blood PEth concentrations would not equal or exceed 20 ng/mL was confirmed. Although the data suggest that regular use of mouthwash is unlikely to result in suprathreshold PEth concentrations, this work highlights the importance of considering extraneous ethanol exposures in clinical decision-making and in future research.
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Affiliation(s)
- Gary M Reisfield
- University of Florida College of Medicine, Department of Psychiatry, UF Health Springhill 1, 4037 NW 86th Terrace, Gainesville, FL 32606, USA
| | - Scott A Teitelbaum
- University of Florida College of Medicine, Department of Psychiatry, Florida Recovery Center, 4001 SW 13th St., Gainesville, FL 32605, USA
| | - Joseph T Jones
- United States Drug Testing Laboratories, Inc., 1700 S. Mt. Prospect Rd., Des Plaines, IL 60018, USA
| | - Dana Mason
- University of Florida College of Medicine, Department of Psychiatry, UF Health Springhill 1, 4037 NW 86th Terrace, Gainesville, FL 32606, USA
| | - Max Bleiweis
- University of Florida College of Medicine, Department of Psychiatry, UF Health Springhill 1, 4037 NW 86th Terrace, Gainesville, FL 32606, USA
| | - Ben Lewis
- University of Florida College of Medicine, Department of Psychiatry, Florida Recovery Center, 4001 SW 13th St., Gainesville, FL 32605, USA
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23
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Skråstad RB, Spigset O, Aamo TO, Andreassen TN. Stability of Phosphatidylethanol 16:0/18:1 in Freshly Drawn, Authentic Samples from Healthy Volunteers. J Anal Toxicol 2021; 45:417-421. [PMID: 32754728 PMCID: PMC8040374 DOI: 10.1093/jat/bkaa082] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 04/12/2020] [Accepted: 05/29/2020] [Indexed: 11/14/2022] Open
Abstract
Due to its specificity, phosphatidylethanol (PEth) 16:0/18:1 has gained increased popularity as a marker for high alcohol consumption in recent years. As conflicting results regarding the stability of PEth 16:0/18:1 in whole blood have been published, there are still uncertainties related to optimum handling, transport and storage of blood samples for the analysis of PEth 16:0/18:1. A stability study where whole blood samples were drawn from healthy volunteers, who had ingested alcohol, is presented. The samples were collected in tubes with ethylenediamine tetraacetic acid (EDTA) and heparin as additives and stored under standardized conditions within 1 h of blood sampling. Storage times were 28 days in ambient temperature and at 4-8°C, and 90 days at -20°C and -80°C. All samples were analyzed regularly during the storage periods. PEth 16:0/18:1 concentrations were stable (defined as < 15% decrease compared with baseline values) at all temperatures up to 28 days, independent of additive. After 90 days of storage at -20°C, the mean concentrations had decreased by 18.8% in EDTA tubes and by 13.8% in heparin tubes. At -80°C, the concentrations were stable throughout the 90-day period. The present study shows that in samples containing PEth formed in vivo, PEth 16:0/18:1 is stable for 28 days irrespective of storage temperature. During long-term storage, samples should be stored at -80°C.
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Affiliation(s)
- Ragnhild Bergene Skråstad
- Department of Clinical Pharmacology, St. Olavs Hospital, 7006 Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
| | - Olav Spigset
- Department of Clinical Pharmacology, St. Olavs Hospital, 7006 Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
| | - Trond Oskar Aamo
- Department of Clinical Pharmacology, St. Olavs Hospital, 7006 Trondheim, Norway
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24
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Aboutara N, Jungen H, Szewczyk A, Sterneck M, Müller A, Iwersen-Bergmann S. Analysis of six different homologues of phosphatidylethanol from dried blood spots using liquid chromatography-tandem mass spectrometry. Drug Test Anal 2020; 13:140-147. [PMID: 32783407 DOI: 10.1002/dta.2910] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/21/2020] [Accepted: 08/05/2020] [Indexed: 12/20/2022]
Abstract
Phosphatidylethanol (PEth) is a direct biomarker for alcohol consumption consisting of a fraction of different ethanol-modified, homologue phospholipids. The aim of this study was to validate an ultra-high-performance liquid chromatography-tandem mass spectrometry method to quantitate six different homologues of PEth (16:0/18:1, 16:0/18:2, 16:0/20:4, 18:0/18:1, 18:0/18:2, and 18:1/18:1) from dried blood spots (DBSs). DBSs were prepared volumetrically (20 μL of whole blood) and extracted with 1 mL of methanol (0.02 ng/μL internal standards). PEth homologues were separated on a BEH C18 column (2.1 × 150 mm, 1.7 μm) using methanol and ammonium acetate buffer (25 mM) in a 7 min isocratic run. Multiple reaction monitoring mode was used for the detection of PEth and the internal standards. Calibrators (10-1000 ng/mL) and quality controls (40, 400, and 700 ng/mL) were prepared from spiked whole blood; external control samples were obtained from proficiency testing schemes. After a comprehensive validation of the method, quantitative patterns of the different homologues were investigated in PEth positive samples (n = 57) from patients in a transplant setting. Satisfactory chromatographic separation, sensitive detection, and reliable quantification of the PEth homologues in DBSs can be achieved using the liquid chromatography-tandem mass spectrometry (LC/MS/MS) procedure. Validation results, including accuracy, linearity, recovery, matrix effects, and in-process stability, complied with international standards, and the analytical performance of the procedure was not affected by the hematocrit of the blood samples. Different quantitative patterns of the investigated PEth homologues were observed in authentic samples from liver transplant patients. This method will enable the study of the kinetics of six PEth homologues simultaneously and investigate the meaning of the homologues' distribution in individuals.
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Affiliation(s)
- Nadine Aboutara
- Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Hilke Jungen
- Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Szewczyk
- Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Sterneck
- Department of Medicine (Med Klinik I), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Alexander Müller
- Department of Legal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
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25
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Neumann J, Beck O, Helander A, Böttcher M. Performance of PEth Compared With Other Alcohol Biomarkers in Subjects Presenting For Occupational and Pre-Employment Medical Examination. Alcohol Alcohol 2020; 55:401-408. [PMID: 32363383 PMCID: PMC7338721 DOI: 10.1093/alcalc/agaa027] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 03/14/2020] [Accepted: 03/24/2020] [Indexed: 01/16/2023] Open
Abstract
Aims To compare the performance of short- and long-term alcohol biomarkers for the evaluation of alcohol drinking in employment-related health controls. Methods The 519 blood samples originated from 509 patients (80% men) presenting at occupational health units and medical centers at employment agencies for the evaluation of risky drinking. The laboratory investigation comprised the measurement of phosphatidylethanol (PEth 16:0/18:1), carbohydrate-deficient transferrin (CDT; % disialotransferrin), gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), ethanol and ethyl glucuronide (EtG). Results Many samples tested positive for acute (57%) and chronic (69%) alcohol biomarkers. PEth was the single most positive biomarker (64%; cut-off 0.05 μmol/l or 35 μg/l) and the only positive chronic biomarker in 100 cases. The highest PEth concentrations were seen in samples positive for all chronic biomarkers, followed by those also being CDT positive (cut-off 2.0%). All 126 CDT-positive samples were positive for PEth using the lower reporting limit (≥0.05 μmol/l) and for 114 cases (90%) also using the higher limit (≥0.30 μmol/l or 210 μg/l). In the CDT-positive cases, the PEth median concentration was 1.71 μmol/l, compared with 0.45 μmol/l for the CDT-negative cases (P < 0.0001). PEth and CDT values were correlated significantly (r = 0.63, P < 0.0001). Among the EtG-positive cases (≥1.0 ng/ml), 95% were also PEth positive, and all ethanol-positive cases (≥0.10 g/l) were also PEth positive. Conclusions For optimal detection of drinking habits, using a combination of short- and long-term alcohol biomarkers provided best information. PEth was the single most positive alcohol biomarker, whereas GGT and MCV offered little additional value over PEth and CDT.
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Affiliation(s)
- Jasna Neumann
- MVZ Labor Dessau GmbH, Bauhüttenstrasse 6, D-06847 Dessau-Roßlau, Germany
| | - Olof Beck
- MVZ Labor Dessau GmbH, Bauhüttenstrasse 6, D-06847 Dessau-Roßlau, Germany.,Department of Clinical Neuroscience, CPF, Norra Stationsgatan 69, Karolinska Institutet, Stockholm, SE-171 77, Sweden
| | - Anders Helander
- Department of Laboratory Medicine, C1:74, Karolinska University Hospital, Karolinska Institutet, Stockholm, SE-141 86, Sweden
| | - Michael Böttcher
- MVZ Labor Dessau GmbH, Bauhüttenstrasse 6, D-06847 Dessau-Roßlau, Germany
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26
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Helander A, Hermansson U, Beck O. Dose-Response Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth)-A Study of Outpatients in Treatment for Reduced Drinking. Alcohol Alcohol 2020; 54:567-573. [PMID: 31529064 DOI: 10.1093/alcalc/agz064] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 06/13/2019] [Accepted: 07/02/2019] [Indexed: 12/25/2022] Open
Abstract
AIM Measurement of whole-blood phosphatidylethanol (PEth) offers high sensitivity and specificity as alcohol biomarker. A remaining issue of importance for the routine application is to better establish the relationship between PEth concentration and amount and duration of drinking. METHODS The study included 36 subjects (32-83 years) voluntarily attending outpatient treatment for reduced drinking. At ~ 3- to 4-week intervals, they provided a diary on their daily alcohol intake and gave blood samples for measurement of PEth and carbohydrate-deficient transferrin (CDT). Whole-blood PEth 16:0/18:1 was measured by liquid chromatography-tandem mass spectrometry and serum CDT (%disialotransferrin) by high-performance liquid chromatography. RESULTS At start, the self-reported past 2-week alcohol intake ranged 0-1260 (median 330) g ethanol, the PEth 16:0/18:1 concentration ranged 0.05-1.20 (median 0.23) μmol/L, and the CDT value ranged 0.7-13.0% (median 1.5%). At the final sampling after 5-20 (median 12) weeks, neither reported alcohol intake nor PEth and CDT levels differed significantly from the starting values. The PEth concentration showed best association with past 2-week drinking, followed by for intake in the next last week. The changes in PEth concentration vs past 2-week alcohol intake between two successive tests revealed that an increased ethanol intake by ~ 20 g/day elevated the PEth concentration by on average ~ 0.10 μmol/L, and vice versa for decreased drinking. CONCLUSIONS The PEth concentration correlated well with past weeks alcohol intake, albeit with a large inter-individual scatter. This indicates that it is possible to make only approximate estimates of drinking based on a single PEth value, implying risk for misclassification between moderate and heavy drinking.
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Affiliation(s)
- Anders Helander
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Division of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.,Division of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
| | - Ulric Hermansson
- Department of Clinical Neurosciences, Karolinska Institutet, Stockholm Centre for Dependence Disorders, Stockholm Health Care Services Riddargatan 1, Stockholm, Sweden
| | - Olof Beck
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Division of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden
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27
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Helander A, Böttcher M, Dahmen N, Beck O. Elimination Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth) in Blood during Alcohol Detoxification. Alcohol Alcohol 2019; 54:251-257. [PMID: 30968936 PMCID: PMC7011165 DOI: 10.1093/alcalc/agz027] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 03/07/2019] [Accepted: 03/15/2019] [Indexed: 11/17/2022] Open
Abstract
Aims The study documented elimination characteristics of three phosphatidylethanol (PEth) homologs in serially collected blood samples from 47 heavy drinkers during ~2 weeks of alcohol detoxification at hospital. Methods Venous whole blood and urine samples were collected every 1–2 days during treatment. Concentrations of PEth, and of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) to detect relapse drinking, were measured using liquid chromatography-tandem mass spectrometry. Results When included in the study, negative or decreasing breath ethanol concentrations demonstrated that the patients were in the elimination phase. The EtG and EtS measurements further confirmed alcohol abstinence during the study, with three exceptions. On admission, all patients tested positive for PEth, the total concentration ranging 0.82–11.7 (mean 6.35, median 5.88) μmol/l. PEth 16:0/18:1, 16:0/18:2 and 16:0/20:4 accounted for on average ~42%, ~26% and ~9%, respectively, of total PEth in these samples. There were good correlations between total PEth and individual homologs (P < 0.0001). There was no significant difference in PEth values between male and female subjects. During abstinence, the elimination half-life values ranged 3.5–9.8 days for total PEth, 3.7–10.4 days for PEth 16:0/18:1, 2.7–8.5 days for PEth 16:0/18:2 and 2.3–8.4 days for PEth 16:0/20:4. Conclusions The results demonstrated a very high sensitivity (100%) of PEth as alcohol biomarker for recent heavy drinking, but considerable differences in the elimination rates between individuals and between different PEth forms. This indicates that it is possible to make only approximate estimates of the quantity and recency of alcohol intake based on a single PEth value.
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Affiliation(s)
- Anders Helander
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
- Clinical Pharmacology and Clinical Chemistry, Karolinska University Laboratory, Stockholm, Sweden
- Corresponding author: C1:74, Clinical Chemistry, Karolinska University Laboratory Huddinge, SE-141 86 Stockholm, Sweden. Tel.: +46-8-58581293; E-mail:
| | | | - Norbert Dahmen
- Universitätsmedizin Mainz, Klinik für Psychiatrie und Psychotherapie, Mainz, Germany
| | - Olof Beck
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
- Clinical Pharmacology and Clinical Chemistry, Karolinska University Laboratory, Stockholm, Sweden
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28
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Stenton J, Walther L, Hansson T, Andersson A, Isaksson A. Inter Individual Variation and Factors Regulating the Formation of Phosphatidylethanol. Alcohol Clin Exp Res 2019; 43:2322-2331. [PMID: 31509266 DOI: 10.1111/acer.14195] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 08/26/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND Alcohol use disorders are a major but often unrecognized health problem. Alcohol markers can therefore be of great value for diagnosis, follow-up, and treatment evaluation. Phosphatidylethanol in blood (B-PEth) is an alcohol biomarker with higher clinical sensitivity and specificity than commonly used alcohol markers but has shown a considerable interindividual variation in relation to reported consumption. METHODS An in vitro system was used to investigate factors, which may affect the formation rate of PEth or which may give rise to interindividual variation in the rate of formation. In this system, isolated erythrocytes from 31 individuals were incubated in the presence of various concentrations of ethanol (EtOH). The concentration of PEth and phosphatidylcholine (PC), the parent molecule of PEth, was determined by chromatographic methods. RESULTS Time, EtOH, and PC concentration were major factors determining the amount of PEth formed. The interindividual variation in PEth formation rate, calculated at an EtOH concentration of 50 mmol/l, showed a coefficient of variation (CV) from 23 to 31% for the different PEth forms studied (PEth 16:0/18:2, total PEth and PEth 16:0/18:1). The concentration of PC was found to be an important determinant of this variation. The formation rate for PEth 16:0/18:2 was somewhat higher than for PEth 16:0/18:1. The formation of PEth 16:0/18:1 but not PEth 16:0/18:2 showed a positive correlation to the concentration of PEth at baseline (endogenous PEth). Calculation of enzyme kinetics for the reaction resulting in the formation of PEth 16:0/18:1 or PEth 16:0/18:2 showed an apparent Km (Michaelis constant) of approximately 160 to 170 mmol/l. CONCLUSIONS Interindividual variation in the formation rate of PEth appears to be a significant but relatively modest source of variation in the relation between B-PEth and reported consumption. Correction for interindividual variation in PC concentrations might substantially reduce the interindividual variability in PEth formation and consequently in B-PEth.
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Affiliation(s)
- Joanna Stenton
- Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, Lund, Sweden
| | - Lisa Walther
- Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, Lund, Sweden
| | - Therese Hansson
- Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, Lund, Sweden
| | - Anders Andersson
- Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, Lund, Sweden
| | - Anders Isaksson
- Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, Lund, Sweden
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29
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Nguyen VL, Fitzpatrick M. Should phosphatidylethanol be currently analysed using whole blood, dried blood spots or both? ACTA ACUST UNITED AC 2019; 57:617-622. [DOI: 10.1515/cclm-2018-0667] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 09/09/2018] [Indexed: 11/15/2022]
Abstract
Abstract
Phosphatidylethanol (PEth) are phospholipids produced through non-oxidative ethanol metabolism. They accumulate in red blood cells and have been traditionally analysed in whole blood as potential biomarkers for moderate to long-term alcohol consumption. More recently, their analysis in dried blood spots has been gaining favour, namely, due to the ease in sampling, transport and storage conditions required. This paper aims at providing a short comparative review between analysing PEth in whole blood and dried blood spots and the potential pitfalls that researchers may face when setting up PEth testing for clinical use.
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30
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Woźniak MK, Wiergowski M, Namieśnik J, Biziuk M. Biomarkers of Alcohol Consumption in Body Fluids - Possibilities and Limitations of Application in Toxicological Analysis. Curr Med Chem 2019; 26:177-196. [PMID: 28982313 DOI: 10.2174/0929867324666171005111911] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 08/08/2016] [Accepted: 09/05/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND Ethyl alcohol is the most popular legal drug, but its excessive consumption causes social problems. Despite many public campaigns against alcohol use, car accidents, instances of aggressive behaviour, sexual assaults and deterioration in labor productivity caused by inebriated people is still commonplace. Fast and easy diagnosis of alcohol consumption is required in order to introduce proper and effective therapy, and is crucial in forensic toxicology analysis. The easiest method to prove alcohol intake is determination of ethanol in body fluids or in breath. However, since ethanol is rapidly metabolized in the human organism, only recent consumption can be detected using this method. Because of that, the determination of alcohol biomarkers was introduced for monitoring alcohol consumption over a wider range of time. OBJECTIVE The objective of this study was to review published studies focusing on the sample preparation methods and chromatographic or biochemical techniques for the determination of alcohol biomarkers in whole blood, plasma, serum and urine. METHODS An electronic literature search was performed to discuss possibilities and limitations of application of alcohol biomarkers in toxicological analysis. RESULTS Authors described the markers of alcohol consumption such as: ethanol, its nonoxidative metabolites (ethyl glucuronide, ethyl sulfate, phosphatidylethanol, ethyl phosphate, fatty acid ethyl esters) and oxidative metabolites (acetaldehyde and acetaldehyde adducts). We also discussed issues concerning the detection window of these biomarkers, and possibilities and limitations of their use in routine analytical toxicology for monitoring alcohol consumption or sobriety during alcohol therapy.
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Affiliation(s)
- Mateusz Kacper Woźniak
- Department of Analytical Chemistry, Faculty of Chemistry, Gdansk University of Technology (GUT), 11/12 Narutowicza Str., Gdansk 80-233, Poland
| | - Marek Wiergowski
- Chair & Department of Forensic Medicine, Faculty of Medicine, Medical University of Gdansk (MUG), 3a M. Skłodowskiej-Curie Str., Gdansk 80-210, Poland
| | - Jacek Namieśnik
- Department of Analytical Chemistry, Faculty of Chemistry, Gdansk University of Technology (GUT), 11/12 Narutowicza Str., Gdansk 80-233, Poland
| | - Marek Biziuk
- Department of Analytical Chemistry, Faculty of Chemistry, Gdansk University of Technology (GUT), 11/12 Narutowicza Str., Gdansk 80-233, Poland
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31
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Chung HW, Petersen EN, Cabanos C, Murphy KR, Pavel MA, Hansen AS, Ja WW, Hansen SB. A Molecular Target for an Alcohol Chain-Length Cutoff. J Mol Biol 2019; 431:196-209. [PMID: 30529033 PMCID: PMC6360937 DOI: 10.1016/j.jmb.2018.11.028] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/30/2018] [Accepted: 11/30/2018] [Indexed: 11/23/2022]
Abstract
Despite the widespread consumption of ethanol, mechanisms underlying its anesthetic effects remain uncertain. n-Alcohols induce anesthesia up to a specific chain length and then lose potency-an observation known as the "chain-length cutoff effect." This cutoff effect is thought to be mediated by alcohol binding sites on proteins such as ion channels, but where these sites are for long-chain alcohols and how they mediate a cutoff remain poorly defined. In animals, the enzyme phospholipase D (PLD) has been shown to generate alcohol metabolites (e.g., phosphatidylethanol) with a cutoff, but no phenotype has been shown connecting PLD to an anesthetic effect. Here we show loss of PLD blocks ethanol-mediated hyperactivity in Drosophila melanogaster (fruit fly), demonstrating that PLD mediates behavioral responses to alcohol in vivo. Furthermore, the metabolite phosphatidylethanol directly competes for the endogenous PLD product phosphatidic acid at lipid-binding sites within potassium channels [e.g., TWIK-related K+ channel type 1 (K2P2.1, TREK-1)]. This gives rise to a PLD-dependent cutoff in TREK-1. We propose an alcohol pathway where PLD produces lipid-alcohol metabolites that bind to and regulate downstream effector molecules including lipid-regulated potassium channels.
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Affiliation(s)
- Hae-Won Chung
- Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA
| | - E Nicholas Petersen
- Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA
| | - Cerrone Cabanos
- Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA
| | - Keith R Murphy
- Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA; Center on Aging, The Scripps Research Institute, Jupiter, FL 33458, USA; Program in Integrative Biology and Neuroscience, Florida Atlantic University, Jupiter, FL 33458, USA
| | - Mahmud Arif Pavel
- Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA
| | - Andrew S Hansen
- HBBiotech, BioInnovations Gateway, Salt Lake City, UT 84115, USA
| | - William W Ja
- Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA; Center on Aging, The Scripps Research Institute, Jupiter, FL 33458, USA
| | - Scott B Hansen
- Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA.
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32
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Casati S, Ravelli A, Angeli I, Durello R, Minoli M, Orioli M. An automated sample preparation approach for routine liquid chromatography tandem-mass spectrometry measurement of the alcohol biomarkers phosphatidylethanol 16:0/18:1, 16:0/16:0 and 18:1/18:1. J Chromatogr A 2018; 1589:1-9. [PMID: 30598290 DOI: 10.1016/j.chroma.2018.12.048] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 12/18/2018] [Accepted: 12/20/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Phosphatidylethanols (PEths) are currently under investigation as highly sensitive and specific direct biomarkers of long-term alcohol abuse. PEths belong to a group of aberrant phospholipids formed in erythrocyte membranes in presence of ethanol by the catalytic action of the enzyme phospholipase D on phosphatidylcholine. Compared to other alcohol biomarkers, a higher sensitivity (94.5-100%) and specificity (100%) characterizes PEth species. METHOD Prior to detection, an important practical aspect in the work-flow of PEths analysis is the sample preparation step. To date, traditional techniques such as liquid-liquid extraction (LLE) and solid phase extraction (SPE) require multiple steps to remove blood interferences. Due to the simplicity of use and the possibility of automation, sample filtration is also a widespread technique in biomedical laboratories. In this work, a reliable sample preparation method based on an automated filtration with Phree™ Phospholipid Removal Plates (Phenomenex, California, USA) was developed to extract PEths from human whole blood. Surface characteristics of Phospholipids Removal material allow phospholipids retention on the filter and a suitable PEths recovery after elution. The blood samples were added with internal standard (IS) and purified in acetonitrile (1 mL). After centrifugation, supernatants were applied to the Phospholipids Removal Plates in an automated workstation. After washing, the phospholipids retained on the filter were eluted with 1-mL 2-propanol 1% ammonia. PEth 16:0/18:1, PEth 16:0/16:0 and PEth 18:1/18:1 were extracted using the proposed method and detected by LC-MS/MS operated in electron spray ionization (ESI). The detection of all compounds was based on multiple reaction monitoring (MRM) transitions. This method was validated for the quantitative profiling of PEth molecular species in human blood collected from heavy and social drinkers. RESULTS The method was validated according to Food and Drug Administration (FDA) guidelines. Linearity was observed in the 25-1250 (PEth 16:0/18:1) and 5-250 (PEth 16:0/16:0 and PEth 18:1/18:1) ng/mL range with a correlation coefficient (r²) between 0.997 and 0.999 for all three compounds. Moreover, the nominal concentrations of non-zero calibrators were ±15%. Variation coefficient (%CV) was < 10% for all the analytes, while lowest limit of quantitation (LLOQ) was found to be 1.25 ng/mL for PEth 16:0/18:1, 0.50 ng/mL for PEth 16:0/16:0 and 0.50 ng/mL for PEth 18:1/18:1. Intra- and inter-day precision and accuracy were always lower than 14% and 11%, respectively. Analytical recovery was higher than 68.8% for all analytes. Sample stability at 4 °C and -20 °C showed a concentration drop lower than 20% up to 4 weeks. Extracts were stable for 7 days in the autosampler and 30 days at -20 °C and 4 °C in a closed vial. The procedure was successfully applied to blood samples collected from heavy drinkers (n = 8), social drinkers (n = 5), and teetotalers (n = 7). CONCLUSIONS Due to the simplicity of application and the possibility of automation, sample filtration is well suited for a clinical and forensic laboratory. To monitor alcohol consumption, an analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) with novel and automated sample preparation was developed and validated for the simultaneous quantification of PEth 16:0/18:1, PEth 16:0/16:0 and PEth 18:1/18:1 in whole blood samples, characterized by a fast sample preparation and lower pre-analysis costs than other extraction procedures.
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Affiliation(s)
- Sara Casati
- Laboratory of Forensic Toxicology, Department of Biomedical, Surgical and Dental Science, University of Milan, Milan, Italy
| | - Alessandro Ravelli
- Laboratory of Forensic Toxicology, Department of Biomedical, Surgical and Dental Science, University of Milan, Milan, Italy
| | - Ilaria Angeli
- Laboratory of Forensic Toxicology, Department of Biomedical, Surgical and Dental Science, University of Milan, Milan, Italy
| | | | - Mauro Minoli
- Laboratory of Forensic Toxicology, Department of Biomedical, Surgical and Dental Science, University of Milan, Milan, Italy
| | - Marica Orioli
- Laboratory of Forensic Toxicology, Department of Biomedical, Surgical and Dental Science, University of Milan, Milan, Italy.
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Berg T, Eliassen E, Jørgenrud B, Kabashi S, Petukhov A, Bogstrand ST. Determination of phosphatidylethanol 16:0/18:1 in whole blood by 96-well supported liquid extraction and UHPLC-MS/MS. J Clin Lab Anal 2018; 33:e22631. [PMID: 30047172 DOI: 10.1002/jcla.22631] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 06/20/2018] [Accepted: 07/05/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Phosphatidylethanols (PEths) are specific, direct alcohol biomarkers that can be determined in human blood to distinguish between heavy and social drinking. PEth 16:0/18:1 is among the most predominant PEth homologues in human blood. The aim of the study was to develop a high throughput and sensitive UHPLC-MS/MS method for the determination of PEth 16:0/18:1 in whole blood. METHODS Whole blood samples were prepared by 96-well supported liquid extraction (SLE). Extracted samples were analyzed for PEth 16:0/18:1 by reversed phase UHPLC-MS/MS. RESULTS The developed UHPLC-MS/MS method was fully validated in whole blood with PEth 16:0/18:1-D5 as internal standard. Intermediate precision and intermediate accuracy were within ≤± 12% and ≤± 17%, respectively, at PEth 16:0/18:1 concentrations of 1.4-2112 ng/mL (2.0-3004 nmol/L). Limit of quantification (LOQ) was 1.7 ng/mL (2.4 nmol/L). CONCLUSION For the first time, 96-well SLE was used for preparation of a PEth homologue in biological samples. A mixture of tert-butyl methyl ether and 2-propanol (5:1, v:v) was chosen as organic eluent based on an evaluation of extraction recovery, purity of extracts, and evaporation time. The developed UHPLC-MS/MS method can be used for high throughput analyses and sensitive determinations of PEth 16:0/18:1 in whole blood.
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Affiliation(s)
- Thomas Berg
- Section of Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway
| | - Elin Eliassen
- Section of Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway
| | - Benedicte Jørgenrud
- Section of Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway
| | - Saranda Kabashi
- Section of Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway
| | - Alexey Petukhov
- Moscow Scientific Practical Center of Drug Addiction, Moscow Municipal Department of Healthcare, Moscow, Russia.,I.M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Stig Tore Bogstrand
- Section of Drug Abuse Research, Department of Forensic Sciences, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.,Lovisenberg Diaconal University College, Oslo, Norway
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34
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Ulwelling W, Smith K. The PEth Blood Test in the Security Environment: What it is; Why it is Important; and Interpretative Guidelines. J Forensic Sci 2018; 63:1634-1640. [DOI: 10.1111/1556-4029.13874] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 06/06/2018] [Accepted: 06/26/2018] [Indexed: 12/29/2022]
Affiliation(s)
- William Ulwelling
- National Security Psychological Services; 2155 Louisiana Blvd, Suite 6500 Albuquerque NM 87110
| | - Kim Smith
- National Security Psychological Services; 2155 Louisiana Blvd, Suite 6500 Albuquerque NM 87110
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Frassinetti S, Moccia E, Caltavuturo L, Gabriele M, Longo V, Bellani L, Giorgi G, Giorgetti L. Nutraceutical potential of hemp (Cannabis sativa L.) seeds and sprouts. Food Chem 2018; 262:56-66. [PMID: 29751921 DOI: 10.1016/j.foodchem.2018.04.078] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 04/18/2018] [Accepted: 04/20/2018] [Indexed: 12/26/2022]
Abstract
In this study the antioxidant effect of Cannabis sativa L. seeds and sprouts (3 and 5 days of germination) was evaluated. Total polyphenols, flavonoids and flavonols content, when expressed on dry weight basis, were highest in sprouts; ORAC and DPPH (in vitro assays), CAA-RBC (cellular antioxidant activity in red blood cells) and hemolysis test (ex vivo assays) evidenced a good antioxidant activity higher in sprouts than in seeds. Untargeted analysis by high resolution mass spectrometry in negative ion mode allowed the identification of main polyphenols (caffeoyltyramine, cannabisin A, B, C) in seeds and of ω-6 (linoleic acid) in sprouts. Antimutagenic effect of seeds and sprouts extracts evidenced a significant decrease of mutagenesis induced by hydrogen peroxide in Saccharomyces cerevisiae D7 strain. In conclusion our results show that C. sativa seeds and sprouts exert beneficial effects on yeast and human cells and should be further investigated as a potential functional food.
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Affiliation(s)
- Stefania Frassinetti
- National Research Council (CNR), Institute of Agricultural Biology and Biotechnology (IBBA), Research Unit of Pisa, Via Moruzzi 1, 56124 Pisa, Italy.
| | - Eleonora Moccia
- National Research Council (CNR), Institute of Agricultural Biology and Biotechnology (IBBA), Research Unit of Pisa, Via Moruzzi 1, 56124 Pisa, Italy
| | - Leonardo Caltavuturo
- National Research Council (CNR), Institute of Agricultural Biology and Biotechnology (IBBA), Research Unit of Pisa, Via Moruzzi 1, 56124 Pisa, Italy
| | - Morena Gabriele
- National Research Council (CNR), Institute of Agricultural Biology and Biotechnology (IBBA), Research Unit of Pisa, Via Moruzzi 1, 56124 Pisa, Italy
| | - Vincenzo Longo
- National Research Council (CNR), Institute of Agricultural Biology and Biotechnology (IBBA), Research Unit of Pisa, Via Moruzzi 1, 56124 Pisa, Italy
| | - Lorenza Bellani
- National Research Council (CNR), Institute of Agricultural Biology and Biotechnology (IBBA), Research Unit of Pisa, Via Moruzzi 1, 56124 Pisa, Italy; Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
| | - Gianluca Giorgi
- Department of Biotechnology, Chemistry and Pharmacy, Via Aldo Moro 2, 53100 Siena, Italy
| | - Lucia Giorgetti
- National Research Council (CNR), Institute of Agricultural Biology and Biotechnology (IBBA), Research Unit of Pisa, Via Moruzzi 1, 56124 Pisa, Italy.
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36
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Study of measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spot (DBS) samples and application of a volumetric DBS device. Clin Chim Acta 2018; 479:38-42. [DOI: 10.1016/j.cca.2018.01.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2017] [Revised: 01/04/2018] [Accepted: 01/04/2018] [Indexed: 12/21/2022]
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37
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Hill-Kapturczak N, Dougherty DM, Roache JD, Karns-Wright TE, Javors MA. Differences in the Synthesis and Elimination of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 After Acute Doses of Alcohol. Alcohol Clin Exp Res 2018; 42:851-860. [PMID: 29505133 DOI: 10.1111/acer.13620] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 02/25/2018] [Indexed: 11/27/2022]
Abstract
BACKGROUND The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers. METHODS A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in 15 minutes. Blood and breath samples were collected before, at various times up to 360 minutes postconsumption, and 2, 4, 7, 11, and 14 days after alcohol consumption. Initial rates of PEth synthesis, 360 minutes area under the PEth pharmacokinetic curves (AUCs), and elimination half-lives were determined. RESULTS (i) Nonzero PEth levels were observed before alcohol dosing for most participants, despite 7 days of alcohol use monitoring; (ii) 0.4 and 0.8 g/kg doses of alcohol produced proportional increases in PEth levels in all but 1 participant; (iii) the initial rate of synthesis of both PEth homologues did not differ between the 2 doses, but was greater for PEth 16:0/18:2 than PEth 16:0/18:1 at both doses; (iv) the mean AUC of both PEth homologues was higher at 0.8 g/kg than at 0.4 g/kg; (v) the mean AUC of 16:0/18:2 was greater than that of PEth 16:0/18:1 at both alcohol doses; (vi) the mean half-life of PEth 16:0/18:1 was longer than that of PEth 16:0/18:2 (7.8 ± 3.3 [SD] days and 6.4 ± 5.0 [SD] days, respectively); and (vii) there were no sex differences in PEth 16:0/18:1 or 16:0/18:2 pharmacokinetics. CONCLUSIONS The results of this study support the use of PEth 16:0/18:1 and 16:0/18:2 as biomarkers for alcohol consumption. Because of consistent pharmacokinetic differences, the levels of these 2 PEth homologues may provide more information regarding the quantity and recentness of alcohol consumption than either alone.
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Affiliation(s)
| | - Donald M Dougherty
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas.,Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
| | - John D Roache
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas.,Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
| | - Tara E Karns-Wright
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas
| | - Martin A Javors
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas.,Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
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38
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Nguyen VL, Haber PS, Seth D. Applications and Challenges for the Use of Phosphatidylethanol Testing in Liver Disease Patients (Mini Review). Alcohol Clin Exp Res 2017; 42:238-243. [DOI: 10.1111/acer.13558] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 11/10/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Van Long Nguyen
- Department of Chemical Pathology; Royal Prince Alfred Hospital; Camperdown New South Wales Australia
- Faculty of Medicine; The University of Sydney; Sydney New South Wales Australia
| | - Paul S. Haber
- Faculty of Medicine; The University of Sydney; Sydney New South Wales Australia
- Drug Health Services; Royal Prince Alfred Hospital; Camperdown New South Wales Australia
| | - Devanshi Seth
- Faculty of Medicine; The University of Sydney; Sydney New South Wales Australia
- Drug Health Services; Royal Prince Alfred Hospital; Camperdown New South Wales Australia
- Centenary Institute of Cancer Medicine and Cell Biology; Camperdown New South Wales Australia
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39
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Isaksson A, Walther L, Hansson T, Andersson A, Stenton J, Blomgren A. High-Throughput LC-MS/MS Method for Determination of the Alcohol Use Biomarker Phosphatidylethanol in Clinical Samples by Use of a Simple Automated Extraction Procedure—Preanalytical and Analytical Conditions. ACTA ACUST UNITED AC 2017; 2:880-892. [DOI: 10.1373/jalm.2017.024828] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 10/30/2017] [Indexed: 11/06/2022]
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40
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Petukhov AE, Nadezhdin AV, Bogstrand ST, Bryun EA, Ramenskaya GV, Koshkina EA, Mel'nik EV, Smirnov AV, Tetenova EY. [The comparative analysis of the methods for the determination of phosphatidylethanol in blood as a biological marker of alcohol abuse]. Sud Med Ekspert 2017; 60:23-26. [PMID: 28980550 DOI: 10.17116/sudmed201760523-26] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The confirmation of the fact of alcohol abuse is currently an important problem of both medical and social significance. Of all biological markers of alcohol consumption presently in use, blood phosphatidylethanol (PEth) is considered to be most sensitive and specific one. Therefore it has promising prospects for the further application. There is no universally accepted method for the calculation of the phosphatidylethanol concentration in human blood. For this reason, the present article places emphasis on the comparative characteristic of various methods for the determination of this substance.
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Affiliation(s)
- A E Petukhov
- Moscow Research and Practical Narcological Centre, Moscow Health Department, Moscow, Russia, 109390; A.P. Arzamastsev Department of Pharmaceutical and Toxicological Chemistry, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia, 119991
| | - A V Nadezhdin
- Moscow Research and Practical Narcological Centre, Moscow Health Department, Moscow, Russia, 109390
| | | | - E A Bryun
- Moscow Research and Practical Narcological Centre, Moscow Health Department, Moscow, Russia, 109390
| | - G V Ramenskaya
- A.P. Arzamastsev Department of Pharmaceutical and Toxicological Chemistry, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia, 119991
| | - E A Koshkina
- Moscow Research and Practical Narcological Centre, Moscow Health Department, Moscow, Russia, 109390
| | - E V Mel'nik
- A.P. Arzamastsev Department of Pharmaceutical and Toxicological Chemistry, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia, 119991
| | - A V Smirnov
- Moscow Research and Practical Narcological Centre, Moscow Health Department, Moscow, Russia, 109390
| | - E Yu Tetenova
- Moscow Research and Practical Narcological Centre, Moscow Health Department, Moscow, Russia, 109390
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41
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Duarte M, Jagadeesan KK, Billing J, Yilmaz E, Laurell T, Ekström S. Solid-phase extraction of the alcohol abuse biomarker phosphatidylethanol using newly synthesized polymeric sorbent materials containing quaternary heterocyclic groups. J Chromatogr A 2017; 1519:1-8. [DOI: 10.1016/j.chroma.2017.08.051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 05/18/2017] [Accepted: 08/19/2017] [Indexed: 01/28/2023]
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42
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Andreassen TN, Havnen H, Spigset O, Falch BMH, Skråstad RB. High Throughput UPLC®-MSMS Method for the Analysis of Phosphatidylethanol (PEth) 16:0/18:1, a Specific Biomarker for Alcohol Consumption, in Whole Blood. J Anal Toxicol 2017; 42:33-41. [DOI: 10.1093/jat/bkx075] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 08/15/2017] [Indexed: 12/11/2022] Open
Affiliation(s)
| | - Hilde Havnen
- Department of Clinical Pharmacology, St. Olav University Hospital, 7006 Trondheim, Norway
| | - Olav Spigset
- Department of Clinical Pharmacology, St. Olav University Hospital, 7006 Trondheim, Norway
- Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway
| | | | - Ragnhild Bergene Skråstad
- Department of Clinical Pharmacology, St. Olav University Hospital, 7006 Trondheim, Norway
- Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway
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43
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Schröck A, Wurst FM, Thon N, Weinmann W. Assessing phosphatidylethanol (PEth) levels reflecting different drinking habits in comparison to the alcohol use disorders identification test - C (AUDIT-C). Drug Alcohol Depend 2017. [PMID: 28645063 DOI: 10.1016/j.drugalcdep.2017.04.026] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
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.
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Affiliation(s)
- Alexandra Schröck
- Institute of Forensic Medicine, Forensic Toxicology and Chemistry, University of Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland
| | - Friedrich M Wurst
- Center for Interdisciplinary Addiction Research Hamburg, Germany; University of Basel, Basel, Switzerland
| | - Natasha Thon
- Paracelsus Medical University, Salzburg, Austria
| | - Wolfgang Weinmann
- Institute of Forensic Medicine, Forensic Toxicology and Chemistry, University of Bern, Switzerland.
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Ullah S, Helander A, Beck O. Identification and quantitation of phosphatidylethanols in oral fluid by liquid chromatography-tandem mass spectrometry. Clin Chem Lab Med 2017; 55:1332-1339. [PMID: 27988502 DOI: 10.1515/cclm-2016-0752] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 10/31/2016] [Indexed: 01/29/2023]
Abstract
BACKGROUND Phosphatidylethanols (PEth) are formed from phosphatidylcholines and ethanol and are used as a specific and sensitive alcohol biomarker. An analytical method for analysis of PEth in oral fluid based on high-performance liquid chromatography coupled to a quadrupole tandem mass spectrometer (LC-MS/MS) was developed and validated and applied on samples collected from patients undergoing alcohol detoxification. METHODS A 200-μL aliquot of oral fluid, collected using the QuantisalTM device, was extracted with chloroform/methanol containing internal standard and subjected to LC-MS/MS analysis of three selected PEth forms (16:0/16:0, 16:0/18:1, and 16:0/18:2). Chromatographic separation was achieved on a UPLC BEH phenyl column, using a mobile phase consisting of acetonitrile and water containing 10 mmol/L ammonium hydrogen carbonate with 0.1% ammonia. The MS instrument was operated in negative electrospray ionization and selected reaction monitoring mode. RESULTS The detection limit for PEth 16:0/16:0, 16:0/18:1, and 16:0/18:2 was ~0.1 ng/mL, and the extraction recoveries at 2.0 ng/mL were in the range of 99%-114%. Method linearity over a concentration range up to 200 ng/mL was ≥0.99. No significant deviation in results was observed in an analyte stability study of two different concentrations at two different temperatures over 3 months. In 35 oral fluid samples collected from patients undergoing alcohol detoxification, the highest concentration was observed for PEth 16:0/18:1 (Detected range, 0.51-55.3 ng/mL; mean, 8.5; median, 3.1). In addition, all three PEth forms were variably identified in a majority (63%) of the oral fluid samples. The PEth 16:0/18:1 values in oral fluid showed a weak positive correlation with the corresponding values in whole blood samples (r=0.50, p=0.026, n=20). CONCLUSIONS The LC-MS/MS method could reliably detect and quantify PEth in oral fluid samples collected after alcohol exposure. The method was characterized by validation data with satisfactory recovery, sensitivity, accuracy, and imprecision, and applied for analysis of clinical samples. The results suggest that measurement of PEth in oral fluid can be used as a biomarker for alcohol consumption, and as such a non-invasive complement to analysis in blood. However, further studies are required to evaluate the test characteristics (e.g. sensitivity and half-life) in comparison with PEth in blood.
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Wang S, Yang R, Ji F, Li H, Dong J, Chen W. Sensitive and precise monitoring of phosphatidylethanol in human blood as a biomarker for alcohol intake by ultrasound-assisted dispersive liquid-liquid microextraction combined with liquid chromatography tandem mass spectrometry. Talanta 2017; 166:315-320. [DOI: 10.1016/j.talanta.2017.01.083] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 01/24/2017] [Accepted: 01/29/2017] [Indexed: 01/15/2023]
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Fleming MF, Smith MJ, Oslakovic E, Lucey MR, Vue JX, Al-Saden P, Levitsky J. Phosphatidylethanol Detects Moderate-to-Heavy Alcohol Use in Liver Transplant Recipients. Alcohol Clin Exp Res 2017; 41:857-862. [PMID: 28196282 DOI: 10.1111/acer.13353] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 02/08/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Alcohol-dependent liver transplantation (LT) patients who resume alcohol consumption are at risk for a number of alcohol-related problems including liver injury and liver failure. Post-LT patients are strongly advised to remain abstinent. However, we do not know how well this population complies due to a lack of valid methods (self-report and/or biomarkers) to identify alcohol use. Studies suggest as many as 50% resume alcohol use within 5 years. Phosphatidylethanol (PEth) is a new cell-membrane phospholipid biomarker to identify alcohol use in the past 28 days. This prospective study followed 213 LT recipients at 2 U.S. liver transplant centers. METHODS Sample included 213 LT subjects; 70.9% (n = 151/213) had a history of alcohol dependence prior to transplantation and 29.1% (n = 62/213) served as non-alcohol-dependent controls. Subjects participated in face-to-face interviews to assess alcohol use using a 30-day calendar. The protocol called for collecting blood samples at baseline, 6-, and 12-month follow-up. RESULTS Seventy percent (149/213) who reported no alcohol use had consistently negative PEth levels (<8 ng/ml). A total of 26.4% (57/213), 44 alcohol-dependent patients and 13 controls, had a positive PEth test of >8 ng/ml either at baseline and/or during the follow-up period. Alcohol-dependent subjects (23.8%; n = 36/151) and 16.1% (n = 10/62) controls reported no alcohol use but had at least 1 positive PEth test. Of the 11.2% (24/213) post-LT subjects who reported recent alcohol use, over half (11/24) had a positive PEth. The 13 self-reported alcohol users with a negative PEth level reported insufficient drinking to trigger PEth formation. CONCLUSIONS Adoption of PEth as part of routine posttransplant care of LT recipients will enable early identification of patients at risk of alcohol use and facilitate abstinence in patients with a history of alcohol dependence and alcohol-related liver damage.
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Affiliation(s)
- Michael Francis Fleming
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Matthew J Smith
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Erika Oslakovic
- Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Michael R Lucey
- Gastroenterology and Hepatology, University of Wisconsin-Madison, Madison, Wisconsin
| | - Jenny X Vue
- Gastroenterology and Hepatology, University of Wisconsin-Madison, Madison, Wisconsin
| | - Patrice Al-Saden
- Transplant Surgery Division (PA-S), Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Josh Levitsky
- Medicine-Gastroenterology and Hepatology and Surgery-Organ Transplantation, Northwestern University, Chicago, Illinois
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47
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Hahn JA, Anton RF, Javors MA. The Formation, Elimination, Interpretation, and Future Research Needs of Phosphatidylethanol for Research Studies and Clinical Practice. Alcohol Clin Exp Res 2016; 40:2292-2295. [PMID: 27716960 DOI: 10.1111/acer.13213] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 08/10/2016] [Indexed: 02/05/2023]
Affiliation(s)
- Judith A Hahn
- Department of Medicine, University of California, San Francisco, California.
| | - Raymond F Anton
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - Martin A Javors
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas
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48
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Walther L, de Bejczy A, Löf E, Hansson T, Andersson A, Guterstam J, Hammarberg A, Asanovska G, Franck J, Söderpalm B, Isaksson A. Phosphatidylethanol is superior to carbohydrate-deficient transferrin and γ-glutamyltransferase as an alcohol marker and is a reliable estimate of alcohol consumption level. Alcohol Clin Exp Res 2016; 39:2200-8. [PMID: 26503066 DOI: 10.1111/acer.12883] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Accepted: 08/20/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND In clinical practice as well as research situations, it is of great importance to get reliable information about a patient's alcohol consumption. The aim of the study was to investigate the correlation of alcohol biomarkers (phosphatidylethanol [PEth], carbohydrate-deficient transferrin [CDT], γ-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase) to retrospective as well as diary-based alcohol self-reports and to examine whether it is possible to correlate a biomarker result to a more precise level of alcohol consumption. METHODS One hundred and sixty alcohol-dependent patients were included in a randomized, placebo-controlled clinical trial of pharmacotherapy for alcohol dependence, of which 115 (76 men and 39 women) completed the study. Retrospective alcohol consumption data were collected at baseline, and alcohol diaries were used during the study. Blood samples for determination of alcohol biomarkers were collected on 5 occasions during the study. RESULTS PEth and CDT showed a better correlation with alcohol consumption documented in the diary (PEth rs = 0.56 and CDT rs = 0.35) than with retrospective consumption data (PEth rs = 0.23 and CDT rs = 0.22). An even higher correlation (rs = 0.63) was seen between the 2 alcohol biomarkers PEth and CDT. At all consumption levels, PEth had the highest sensitivity of all biomarkers studied. CONCLUSIONS PEth was the biomarker with the best correlation to self-reported alcohol consumption. PEth was superior to CDT owing to its substantially higher sensitivity but also due to its closer correlation to self-report. PEth values can be translated into an approximate level of alcohol consumption and PEth appears to be a more reliable measure of alcohol consumption than self-reports.
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Affiliation(s)
- Lisa Walther
- Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, University Hospital, Lund University, Lund, Sweden
| | - Andrea de Bejczy
- Addiction Biology Unit, Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Elin Löf
- Addiction Biology Unit, Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Therese Hansson
- Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, University Hospital, Lund University, Lund, Sweden
| | - Anders Andersson
- Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, University Hospital, Lund University, Lund, Sweden
| | - Joar Guterstam
- Department of Clinical Neuroscience , Karolinska Institutet, Stockholm, Sweden
| | - Anders Hammarberg
- Department of Clinical Neuroscience , Karolinska Institutet, Stockholm, Sweden
| | - Gulber Asanovska
- Department of Clinical Alcohol Research , Malmö University Hospital, Lund University, Lund, Sweden
| | - Johan Franck
- Department of Clinical Neuroscience , Karolinska Institutet, Stockholm, Sweden
| | - Bo Söderpalm
- Addiction Biology Unit, Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anders Isaksson
- Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, University Hospital, Lund University, Lund, Sweden
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49
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Alternative sampling strategies for the assessment of alcohol intake of living persons. Clin Biochem 2016; 49:1078-91. [PMID: 27208822 DOI: 10.1016/j.clinbiochem.2016.05.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 04/28/2016] [Accepted: 05/01/2016] [Indexed: 01/16/2023]
Abstract
Monitoring of alcohol consumption by living persons takes place in various contexts, amongst which workplace drug testing, driving under the influence of alcohol, driving licence regranting programs, alcohol withdrawal treatment, diagnosis of acute intoxication or fetal alcohol ingestion. The matrices that are mostly used today include blood, breath and urine. The aim of this review is to present alternative sampling strategies that allow monitoring of the alcohol consumption in living subjects. Ethanol itself, indirect (carbohydrate deficient transferrin, CDT%) as well as direct biomarkers (ethyl glucuronide, EtG; ethyl sulphate, EtS; fatty acid ethyl esters, FAEEs and phosphatidylethanol species, PEths) of ethanol consumption will be considered. This review covers dried blood spots (CDT%, EtG/EtS, PEths), dried urine spots (EtG/EtS), sweat and skin surface lipids (ethanol, EtG, FAEEs), oral fluid (ethanol, EtG), exhaled breath (PEths), hair (EtG, FAEEs), nail (EtG), meconium (EtG/EtS, FAEEs), umbilical cord and placenta (EtG/EtS and PEth 16:0/18:1). Main results, issues and considerations specific to each matrix are reported. Details about sample preparation and analytical methods are not within the scope of this review.
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50
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Javors MA, Hill-Kapturczak N, Roache JD, Karns-Wright TE, Dougherty DM. Characterization of the Pharmacokinetics of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 in Human Whole Blood After Alcohol Consumption in a Clinical Laboratory Study. Alcohol Clin Exp Res 2016; 40:1228-34. [PMID: 27130527 DOI: 10.1111/acer.13062] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Accepted: 03/06/2016] [Indexed: 11/30/2022]
Abstract
BACKGROUND The purpose of this study was to characterize the pharmacokinetics of 2 homologues of phosphatidylethanol (PEth) and their combined total in uncoagulated, whole blood samples taken from participants in a human clinical laboratory study after consumption of low doses of ethanol (EtOH). METHODS As part of a larger study, 14 male and 13 female participants received either 0.25 or 0.50 g/kg oral doses of EtOH during a 15-minute period. Blood samples were collected before and throughout 6 hours after each EtOH dose on the day of consumption and then every 3 days during the next 14 days. PEth 16:0/18:1 and PEth 16:0/18:2 levels were quantified in blood samples by HPLC/MS/MS and reported separately or as their combined total (combined PEth). Breath alcohol concentrations (BrACs) were measured concurrently with each blood collection. Transdermal alcohol concentrations were measured every 30 minutes during the entire 22-day study to confirm the absence of drinking during a 7-day period before and the 14-day period after EtOH consumption. RESULTS (i) Single doses of 0.25 and 0.50 g EtOH/kg produced proportional increases in BrAC and combined PEth levels of all participants; (ii) the areas under the curve (AUCs) for each participant's BrAC levels during the 6-hour period after EtOH administration were correlated with AUCs of cPEth (calculated as the AUC of the increase above baseline for combined PEth); (iii) the mean half-life of combined PEth, determined during the 14-day period after EtOH consumption, was 4.6 ± 3.5 (SD) days (range: 1.0 to 13.1 days). CONCLUSIONS Combined PEth is a sensitive biomarker for the identification of relatively low levels of EtOH consumption. The measurement of these 2 homologues may provide additional sensitivity to identify low levels of drinking.
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Affiliation(s)
- Martin A Javors
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas.,Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
| | | | - John D Roache
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas.,Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
| | - Tara E Karns-Wright
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas
| | - Donald M Dougherty
- Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas.,Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas
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