Fortschr Neurol Psychiatr 2013; 81(9): 493-502
DOI: 10.1055/s-0033-1335586
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Direkte Ethanolmetaboliten als Biomarker für Alkoholkonsum: Grundlagen und Anwendungen

Direct Metabolites of Ethanol as Biological Markers of Alcohol Use: Basic Aspects and Applications
N. Thon
1   Universitätsklinik für Psychiatrie und Psychotherapie II, Christian-Doppler-Klinik, Paracelsus Medizinische Privatuniversität Salzburg
,
W. Weinmann
2   Institut für Rechtsmedizin, Universität Bern
,
M. Yegles
3   Laboratoire National de Santé – Toxicologie, Universität Luxemburg
,
U. Preuss
4   Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Kreiskrankenhaus Prignitz gemeinnützige GmbH, Perleberg
,
F. M. Wurst
1   Universitätsklinik für Psychiatrie und Psychotherapie II, Christian-Doppler-Klinik, Paracelsus Medizinische Privatuniversität Salzburg
› Author Affiliations
Further Information

Publication History

Publication Date:
15 July 2013 (online)

Zusammenfassung

Biomarker sind in Diagnose und Therapie alkoholbezogener Störungen in Ergänzung zu Selbstangaben von relevanter Bedeutung. Traditionelle Biomarker wie Gamma-Glutamyltranspeptidase (GGT) und mittleres korpuskuläres Volumen (MCV) sind indirekte Marker und werden durch Alter, Geschlecht und nicht alkoholbezogene Erkrankungen beeinflusst. Direkte Ethanolmetabolite wie Ethylglukuronid (EtG), Ethylsulfat (EtS) und Phosphatidylethanol (PEth) sind direkte Stoffwechselprodukte von Alkohol. Sie zeichnen sich durch hohe Sensitivität und Spezifität aus, decken ein komplementäres Zeitfenster des Konsumnachweises ab und werden seit einigen Jahren zunehmend routinemäßig eingesetzt. Direkte Ethanolmetabolite sind im Serum für Stunden, im Urin für bis zu 7 Tage, im Vollblut über 2 Wochen und in Haaren über Monate nachweisbar. Zu den Anwendungsbereichen gehören klinisch routinemäßige Anwendungen, der Einsatz in notfallmedizinischen Kontexten, Abstinenznachweis in Alkoholbehandlungsprogrammen, bei Fahreignungsuntersuchungen, Lebertransplantationen, betrieblicher Gesundheitsprävention sowie die Verwendung zur Abschätzung des Alkoholkonsums während der Schwangerschaft im Zusammenhang mit dem fetalen Alkohol-Syndrom. Durch ihre Eigenschaften eröffnen sie neue Perspektiven in Prävention, interdisziplinärer Kooperation, Diagnose und Therapie alkoholbezogener Störungen.

Abstract

In addition to self reports and questionnaires, biomarkers are of relevance in the diagnosis of and therapy for alcohol use disorders. Traditional biomarkers such as gamma-glutamyl transpeptidase or mean corpuscular volume are indirect biomarkers and are subject to the influence of age, gender and non-alcohol related diseases, among others. Direct metabolites of ethanol such as ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth) are direct metabolites of ethanol, that are positive after intake of ethyl alcohol. They represent useful diagnostic tools for identifying alcohol use even more accurately than traditional biomarkers. Each of these drinking indicators remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake – EtG and EtS in urine up to 7 days, EtG in hair for months after ethanol has left the body. Applications include clinical routine use, emergency room settings, proof of abstinence in alcohol rehabilitation programmes, driving under influence offenders, workplace testing, assessment of alcohol intake in the context of liver transplantation and foetal alcohol syndrome. Due to their properties, they open up new perspectives for prevention, interdisciplinary cooperation, diagnosis of and therapy for alcohol-related problems.

 
  • Literatur

  • 1 Pabst A, Kraus L. Alkoholkonsum, alkoholbezogene Störungen und Trends. Ergebnisse des Epidemiologischen Suchtsurveys 2006. Sucht 2008; 54: 36-46
  • 2 Mann K. Neue ärztliche Aufgaben bei Alkoholproblemen: von der Behandlungskette zum Behandlungsnetz. Deutsches Ärzteblatt 2002; 99 (10) 632-644
  • 3 Tonnesen H, Kehlet H. Preoperative alcoholism and postoperative morbidity. Br J Surg 1999; 86 (07) 869-874
  • 4 Spies C, Tonnesen H, Andreasson S et al. Perioperative morbidity and mortality in chronic alcoholic patients. Alcohol Clin Exp Res 2001; 25 (05) 164S-170
  • 5 Rubinsky AD, Sun H, Blough DK et al. AUDIT-C alcohol use screening results and postoperative inpatient health care use. J Am Coll Surg 2012; 214 (03) 296-305
  • 6 Rehm J, Mathers C, Popova S et al. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol use disorders. The Lancet 2009; 373: 2223-2233
  • 7 DHS;. http://www.dhs.de/web/datenfakten/alkohol.php [Zugriff am 6.12.2012]
  • 8 Moore RD, Bone LR, Geller G et al. Prevalence, detection, and treatment of alcoholism in hospitalized patients. JAMA 1989; 261: 403-407
  • 9 World Health Organisation (WHO). Global Status Report on Alcohol and Health 2011. http://www.who.int/substance_abuse/publications/global_alcohol_report/en/ Zugriff am 23.7.2012)
  • 10 Ewing JA. Detecting alcoholism: The CAGE questionnaire. J Am Med Assoc 1984; 252: 1905-1907
  • 11 Saunders JB, Aasland OG, Babor TF et al. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption – II. Addiction 1993; 88: 791-804
  • 12 Conigrave KM, Degenhardt LJ, Whitfield B et al. On behalf of the WHO/ISBRA study on biological state and trait markers of alcohol use and dependence investigators. CDT, GGT, and AST as markers of alcohol use: The WHO/ISBRA collaborative project. Alcohol Clin Exp Res 2002; 26: 332-339
  • 13 Laposata M. Assessment of ethanol intake – current tests and new assays on the horizon. Am J Clin Pathol 1999; 112: 443-450
  • 14 Helander A. Biological markers in alcoholism. J Neural Transm 2003; 66: 15-32
  • 15 Hannuksela ML, Liisanantti MK, Nissinen AE et al. Biochemical markers of alcoholism. Clin Chem Lab Med 2007; 45: 953-961
  • 16 Niemelä O. Biomarkers in alcoholism. Clin Chim Acta 2007; 377: 39-49
  • 17 Allen JP, Marques P, Wurst F. Biomarkers of alcohol use: their nature, strengths, and limitations. Mil Med 2009; 173 (08) v-viii
  • 18 Alt A, Janda I, Seidl S et al. Determination of ethyl glucuronide in hair samples. Alcohol Alcohol 2000; 35: 313-314
  • 19 Dahl H, Stephanson N, Beck O et al. Comparison of urinary excretion characteristics of ethanol and ethyl glucuronide. J Anal Toxicol 2002; 26: 201-204
  • 20 Dahl H, Voltaire CarlssonA, Hillgren K et al. Urinary ethyl glucuronide and ethyl sulfate testing for detection of recent drinking in an outpatient treatment program for alcohol and drug dependence. Alcohol Alcohol 2011; 46 (03) 278-282
  • 21 Schmitt G, Aderjan R, Keller T et al. Ethyl-Glucuronide: An unusual ethanolmetabolite in humans. Synthesis, analytical data, and determination in serum and urine. J Anal Toxicol 1995; 19: 91-94
  • 22 Skipper GE, Schaefer P, Thierauf A et al. Detection of Surreptitious Alcohol Use Among Health Professionals Recovering from Substance-Related Disorders Using a New Marker, Ethyl Glucuronide. Alcohol Alcohol 2004; 39: 445-459
  • 23 Schlögel H, Dresen S, Spaczynski K et al. Stability of ethyl glucuronide in urine, post-mortem tissue and blood samples. Int J Legal Med 2005; 30: 1-6
  • 24 Wurst FM, Kempter C et al. Ethyl glucuronide – a marker of alcohol consumption and a relapse marker with clinical and forensic implications. Alcohol Alcohol 1999; 34: 71-77
  • 25 Wurst FM, Kempter Ch, Seidl S et al. Can ethyl glucuronide be determined in post mortem body fluids and tissues?. Alcohol Alcohol 1999; 34: 262-263
  • 26 Wurst FM, Metzger JW on behalf of the WHO/ISBRA study on biological state and trait markers of alcohol use and dependence . The direct ethanol metabolite Ethyl glucuronide is a useful marker of recent alcohol consumption. Alcohol Clin Exp Res 2002; 26: 1114-1119
  • 27 Wurst FM, Vogel R, Jachau K et al. Ethyl glucuronide detects recent alcohol use in forensic psychiatric inpatients. Alcohol Clin Exp Res 2003; 27: 471-476
  • 28 Wurst FM, Skipper GE, Weinmann W. Ethyl glucuronide – the direct ethanol metabolite on the threshold from science to routine use. Addiction 2003; 98 (Suppl. 02) 51-61
  • 29 Wurst FM, Wiesbeck GA, Metzger JW et al. on behalf of the WHO/ISBRA study on biological state and trait markers of alcohol use and dependence. On sensitivity, specificity and the influence of various parameters on ethyl glucuronide levels in urine – Results from the WHO/ISBRA Study. Alcohol Clin Exp Res 2004; 28: 1220-1228
  • 30 Wurst FM, Kelso E, Weinmann W et al. Measurement of Direct Ethanol Metabolites suggests Higher Rate of Alcohol Use among Pregnant Women than found with the AUDIT – a Pilot Study in a Population-Based Sample of Swedish Women. Am J Obstet Gynecol 2008; 198 (04) 407.e1-5
  • 31 Wurst FM, Dürsteler-MacFarland KM, Auwaerter V et al. Assessment of alcohol use among methadone maintenance patients by direct ethanol metabolites and self-reports. Alcohol Clin Exp Res 2008; 32: 1552-1557
  • 32 Wurst FM, Yegles M, Alling C et al. Measurement of direct ethanol metabolites in a case of a former driving under influence (DUI) of alcohol offender, now claming abstinence. Int J Legal Med 2008; 122: 235-239
  • 33 Wurst FM, Haber PS, Wiesbeck G et al. Assessment of alcohol consumption among hepatitis C positive people receiving opioid maintenance treatment using direct ethanol metabolites and self report – a pilot study. Addict Biol 2008; 13: 416-422
  • 34 Wurst FM, Thon N, Yegles M et al. Optimizing heroin-assisted treatment (HAT): assessment of the contribution of direct ethanol metabolites in identifying hazardous and harmful alcohol use. Drug Alcohol Depend 2011; 115 (01) 57-61
  • 35 Politi L, Morini L, Leone F et al. Ethyl glucuronide in hair: Is it a reliable marker of chronic high levels of alcohol consumption?. Addiction 2006; 101: 1408-1412
  • 36 Junghanns K, Graf I, Pflüger J et al. Urinary ethyl glucuronide (EtG) and ethyl sulphate (EtS) assessment: valuable tools to improve verification of abstention in alcohol-dependent patients during in-patient treatment and at follow-ups. Addiction 2009; 104: 921-926
  • 37 Halter CC, Dresen S, Auwaerter V et al. Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake. Int J Legal Med 2008; 122: 123-128
  • 38 Wiens F, Zitztmann A, Lachance MA et al. Chronic intake of fermented floral nectar by wild treeshrews. PNAS 2008; 105: 10426-10431
  • 39 Albermann ME, Musshoff F, Aengenheister L et al. Investigations on the influence of different grinding procedures on measured ethyl glucuronide concentrations in hair determined with an optimized and validated LC-MS/MS method. Anal Bioanal Chem 2012; 403 (03) 769-776
  • 40 Ferreira LM, Binz T, Yegles M. The influence of ethanol containing cosmetics on ethyl glucuronide concentration in hair. Forensic Sci Int 2012; 218: 123-125
  • 41 Hoiseth G, Nordal K, Pettersen E et al. Prolonged urinary detection times of EtG and EtS in patients with decreased renal function. Alcohol Clin Exp Res 2012; 36 (07) 1148-1151
  • 42 Høiseth G, Morini L, Ganss R et al. Higher Levels of Hair Ethyl Glucuronide in Patients with Decreased Kidney Function. Alcohol Clin Exp Res 2012; [Epub ahead of print]
  • 43 Hagström H, Stål P, Stokkeland K et al. Alcohol consumption in patients with primary sclerosing cholangitis. World J Gastroenterol 2012; 18: 3105-3111
  • 44 McDonell MG, Howell DN, McPherson S et al. Voucher-based reinforcement for alcohol abstinence using the ethyl-glucuronide alcohol biomarker. J Appl Behav Anal 2012; 45 (01) 161-165
  • 45 Stewart SH, Koch DG, Burgess DM et al. Sensitivity and Specificity of Urinary Ethyl Glucuronide and Ethyl Sulfate in Liver Disease Patients. Alcohol Clin Exp Res 2012; [Epub ahead of print]
  • 46 Redondo AH, Körber C, König S et al. Inhibition of bacterial degradation of EtG by collection as dried urine spots (DUS). Anal Bioanal Chem 2012; 402 (07) 2417-2424
  • 47 Dresen S, Weinmann W, Wurst FM. Forensic confirmatory analysis of ethyl sulfate – a new marker for alcohol consumption – by liquid chromatography/electrospray ionisation/tandem mass spectrometry. J Americ Soc Mass Spectrom 2004; 15: 1644-1648
  • 48 Helander A, Beck O. Mass Spectrometric Identification of Ethyl Sulfate as an Ethanol Metabolite in Humans. Clin Chem 2004; 5: 936-937
  • 49 Wurst FM, Dresen S, Allen JP et al. Ethyl Sulphate: A Direct Ethanol Metabolite Reflecting Recent Alcohol Consumption. Addiction 2006; 101: 204-211
  • 50 Alling C, Gustavsson L, Änggård E. An abnormal phospholipid in rat organs after ethanol. FEBS Lett 1983; 152: 24-28
  • 51 Aradottir S, Asanovska G, Gjerss S et al. Phosphatidylethanol (PEth) concentrations in blood are correlated to reported alcohol intake in alcohol-dependent patients. Alcohol Alcohol 2006; 41: 431-437
  • 52 Varga A, Hansson P, Lundqvist C et al. Phosphatidylethanol in blood as a marker of ethanol consumption in healthy volunteers: comparison with other markers. Alcohol Clin Exp Res 1998; 22: 1832-1837
  • 53 Hartmann S, Aradottir S, Graf M et al. Phosphatidylethanol as a sensitive and specific biomarker – comparison with gamma glutamyl transpeptidase, mean corpuscular volume and carbohydrate-deficient transferrin. Addict Biol 2007; 12: 81-84
  • 54 Marques P, Tippets S, Allen JP et al. Estimating Driver Risk Using Alcohol Biomarkers, Interlock BAC Tests and Psychometric Assessments. Addiction 2010; 105 (02) 226-239
  • 55 Marques P, Hansson T, Isaksson A et al. Detection of phosphatidylethanol (PEth) in the blood of drivers in an alcohol ignition interlock program. Traffic Inj Prev 2011; 12 (02) 136-141
  • 56 Kip MJ, Spies CD, Neumann T et al. The usefulness of direct ethanol metabolites in assessing alcohol intake in nonintoxicated male patients in an Emergency Room setting. Alcohol Clin Exp Res 2008; 32: 1284-1291
  • 57 Gnann H, Weinmann W, Engelmann C et al. Selective detection of phosphatidylethanol homologues in blood as biomarkers for alcohol misuse by LC-ESI-MS/MS. J Mass Spectrom 2009; 44 (09) 1293-1299
  • 58 Gnann H, Weinmann W, Thierauf A. Formation of Phosphatidylethanol and Its Subsequent Elimination During an Extensive Drinking Experiment Over 5 Days. Alcohol Clin Exp Res 2012; 36 (09) 1507-1511
  • 59 Zheng Y, Beck O, Helander A. Method development for routine liquid chromatography-mass spectrometry measurement of the alcohol biomarker phosphatidylethanol (PEth) in blood. Clin Chim Acta 2011; 412: 1428-1435
  • 60 Nissinen AE, Laitinen LM, Kakko S et al. Low plasma antibodies specific for phosphatidylethanol in alcohol abusers and patients with alcoholic pancreatitis. Addict Biol 2012; 17 (06) 1057-1067
  • 61 Isaksson A, Walther L, Hansson T et al. Phosphatidylethanol in blood (B-PEth): a marker for alcohol use and abuse. Drug Test Anal 2011; 3: 195-200
  • 62 Wurst FM, Thon N, Aradottir S et al. Phosphatidylethanol: normalization during detoxification, gender aspects and correlation with other biomarkers and self-reports. Addict Biol 2010; 15 (01) 88-95
  • 63 Wurst FM, Thon N, Weinmann W et al. Characterization of sialic acid index of plasma apolipoprotein J and phosphatidylethanol during alcohol detoxification – a pilot study. Alcohol Clin Exp Res 2012; 36 (02) 251-257
  • 64 Loftus N, Barnes A, Ashton S et al. Metabonomic investigation of liver profiles of nonpolar metabolites obtained from alcohol-dosed rats and mice using high mass accuracy MSn analysis. J Proteome Res 2011; 10 (02) 705-713
  • 65 Stewart SH, Reuben A, Brzezinski WA et al. Preliminary evaluation of phosphatidylethanol and alcohol consumption in patients with liver disease and hypertension. Alcohol Alcohol 2009; 44 (05) 464-467
  • 66 Stewart SH, Law TL, Randall PK et al. Phosphatidylethanol and alcohol consumption in reproductive age women. Alcohol Clin Exp Res 2010; 34 (03) 488-492
  • 67 Faller A, Richter B, Kluge M et al. LC-MS/MS analysis of phosphatidylethanol in dried blood spots versus conventional blood specimens. Anal Bioanal Chem 2011; 401 (04) 1163-1166
  • 68 Auwärter V, Sporkert F, Hartwig S et al. Fatty acid ethyl esters in hair as markers of alcohol consumption. Segmental hair analysis of alcoholics, social drinkers, and teetotalers. Clin Chem 2001; 47: 2114-2123
  • 69 Pragst F, Auwaerter V, Sporkert F et al. Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). Forensic Sci Int 2001; 121: 76-88
  • 70 Appenzeller BMR, Agirman R, Neuberg P et al. Segmental determination of ethyl glucuronide in hair: A pilot study. Forensic Sci Int 2007; 173: 87-92
  • 71 Pragst F, Yegles M. Alcohol markers in hair. In: Kintz P, (Hrsg.) Analytical and pratical aspects drug testing in hair. Boca Raton, London, New York: CRC Press Taylor & Francis; 2007: 287-324
  • 72 Foti RS, Fisher MB. Assessment of UDP-glucuronosyltransferase catalyzed formation of ethyl glucuronide in human liver microsomes and recombinant UGTs. Forensic Sci Int 2005; 153 (02) 109-116
  • 73 Neubauer O. Über Glucuronsäurepaarung bei Stoffen der Fettreihe. Archiv für experimentelle und pathologische Pharmakologie 1901; 46: 133-154
  • 74 Borucki K, Schreiner R, Dierkes J et al. Detection of recent ethanol intake with new markers: comparison of fatty acid ethyl esters in serum and of ethyl glucuronide and the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid in urine. Alcohol Clin Exp Res 2005; 29: 781-787
  • 75 Helander A, Hagelberg CA, Beck O et al. Case report. Unreliable alcohol testing in a shipping safety programme. Forensic Sci Int 2009; 189: e45-e47
  • 76 Thierauf A, Halter CC, Rana S et al. Urine tested positive for ethyl glucuronide after trace amounts of ethanol. Addiction 2009; 104 (12) 2007-2012
  • 77 Costantino A, Digregorio EJ, Korn W et al. The effect of the use of mouthwash on ethylglucuronide concentration in urine. J Anal Toxicol 2006; 30: 659-662
  • 78 Rohrig TP, Huber C, Goodson L et al. Detection of ethylglucuronide in urine following the application of Germ-X. J Anal Toxicol 2006; 30 (09) 703-704
  • 79 Thierauf A, Wohlfarth A, Auwärter V et al. Urine tested positive for ethyl glucuronide and ethyl sulfate after the consumption of yeast and sugar. Forensic Sci Int 2010; 202: 1-3
  • 80 Gitto S, Micco L, Conti F et al. Alcohol and viral hepatitis: A mini-review. Digestive and Liver Disease 2009; 41: 67-70
  • 81 Safdar K, Schiff ER. Alcohol and hepatitis C. Semin Liver Dis 2004; 24 (03) 305-315
  • 82 Dahl H, Hammarberg A, Franck J et al. Urinary ethyl glucuronide and ethyl sulfate testing for recent drinking in alcohol-dependent outpatients treated with acamprosate or placebo. Alcohol Alcohol 2011; 46 (05) 553-557
  • 83 Mitchell JM, Teague CH, Kayser AS et al. Varenicline decreases alcohol consumption in heavy-drinking smokers. Psychopharmacology 2012; 223 (03) 299-306
  • 84 Burroughs AK, Sabin CA, Rolles K et al. 3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome. Lancet 2006; 367: 225-232
  • 85 Kelly M, Chick J, Gribble R et al. Predictors of relapse to harmful alcohol after orthotopic liver transplantation. Alcohol Alcohol 2006; 41: 278-283
  • 86 DiMartini A, Day N, Dew MA et al. Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease. Liver Transpl 2006; 12: 813-820
  • 87 Böttcher M, Beck O, Helander A. Evaluation of a new immunoassay for urinary ethyl glucuronide testing. Alcohol Alcohol 2008; 43: 46-48
  • 88 Erim Y, Bottcher M, Dohmen U et al. Urinary ethyl glucuronide testing detects alcohol consumption in alcoholic liver disease patients awaiting liver transplantation. Liver Transpl 2007; 13: 757-761
  • 89 Webzell I, Ball D, Bell J et al. Substance use by liver transplant candidates: an anonymous urinalysis study. Liver Transpl 2011; 17 (10) 1200-1204
  • 90 Aderjan R, Babel B, Briellmann T et al. Anlage zu den Richtlinien der GTFCh zur Qualitätssicherung bei forensisch-toxikologischen Untersuchungen. Anhang A: Anforderung an einzelne Analysenmethoden. Toxichem Krimtech 2000; 67: 13-16
  • 91 Weinmann W, Schäfer P, Thierauf A et al. Confirmatory analysis for ethyl glucuronide in urine by liquid chromatography/electrospray tandem mass spectrometry applying forensic guidelines. J Am Soc Mass Spectrom 2004; 15: 188-193
  • 92 Kaufmann E, Alt A. Detection of ethyl glucuronide in dried human blood using LC-MS/MS. Int J Legal Med 2008; 122: 245-249
  • 93 Winkler M, Kaufmann E, Thoma D et al. Detection of ethyl glucuronide in blood spotted on different surfaces. Forensic Science International 2011; 210: 243-246
  • 94 Helander A, Dahl H. Urinary tract infection: a risk factor for false-negative urinary ethyl glucuronide but not ethyl sulfate in the detection of recent alcohol consumption. Clin Chem 2005; 51 (09) 1728-1730
  • 95 Baranowski S, Serr A, Thierauf A. In vitro study of bacterial degradation of ethyl glucuronide and ethyl sulfate. Int J Leg Med 2008; 122: 389-393
  • 96 Halter CC, Laengin A, Al-Ahmad A et al. Assessment of the stability of the ethanol metabolite ethyl sulfate in standardised degradation tests. Forensic Sci Int 2009; 186 (01) 52-55
  • 97 Boström H, Vestermark A. Studies on ester sulfates. 7. On the excretion of sulphate conjugates of primary aliphatic alcohols in the urine of rats. Acta Physiol Scand 1960; 48: 88-94
  • 98 Schneider H, Glatt H. Sulfo conjugation of ethanol in humans in vivo and by individual sulfotransferase forms in vitro. Biochem J 2004; 383: 543
  • 99 Society of Forensic Toxicologists and American Academy of Forensic Sciences, SOFT/AAFS. Forensic Toxicology Laboratory Guidelines. 2006 ( http://www.soft-tox.org/index.php?option=com_content&view=article&id=55&Itemid=62 , accessed July 22, 2012)
  • 100 SAMHSA. Mandatory Guidelines for Federal Workplace Drug Testing. Federal Register, 2004 69/81. 19644-19673 http://www.workplace.samhsa.gov/DrugTesting/Level_1_Pages/HHS%20Mandatory%20Guidelines%20 (Effective%20November%201,%202004).aspx accessed December 22, 2004).
  • 101 Albermann ME, Musshoff F, Doberentz E et al. Preliminary investigations on ethyl glucuronide and ethyl sulfate cutoffs for detecting alcohol consumption on the basis of an ingestion experiment and on data from withdrawal treatment. Int J Legal Med 2012; 126 (05) 757-764
  • 102 Tsujita T, Okuda H. Fatty acid ethyl ester synthase in rat adipose tissue and its relationship to carboxylesterase. J Biol Chem 1992; 267: 23489-23494
  • 103 Bora PS, Guruge DG, Miller DD et al. Purification and charac­terization of human heart fatty acid ethyl ester synthase/carboxylesterase. J Mol Cell Cardiol 1996; 28: 2027-2032
  • 104 Bora PS, Spilburg CA, Lange LG. Metabolism of ethanol and carcinogens by glutathione transferases. Prot Natl Acad Sci USA 1989; 86: 4470-4473
  • 105 Chang W, Waltenbaugh C, Borensztajn J. Fatty acid ethyl ester synthesis by isolated perfu­sed rat heart. Metabolism 1997; 46: 926-929
  • 106 Pragst F, Yegles M. Determination of fatty acid ethyl esters (FAEE) and ethyl flucuronide (EtG) in hair: a promising way for retrospective detection of alcohol abuse during pregnancy?. Ther Drug Monit 2008; 30: 255-263
  • 107 Yegles M, Labarthe A, Auwärter V et al. Comparison of ethyl glucuronide and fatty acid ethyl ester concentrations in hair of alcoholics, social drinkers and teetotallers. Forensic Sci Int 2004; 145: 167-173
  • 108 González-Illán F, Ojeda-Torres G, Díaz-Vázquez LM et al. Detection of fatty acid ethyl esters in skin surface lipids as biomarkers of ethanol consumption in alcoholics, social drinkers, light drinkers, and teetotalers using a methodology based on microwave-assisted extraction followed by solid-phase microextraction and gas chromatography-mass spectrometry. J Anal Toxicol 2011; 35 (04) 232-237
  • 109 Gustavsson L, Alling C. Formation of phosphatidylethanol in rat brain by phospholipase D. Biochem Biophys Res Commun 1987; 142: 958-963
  • 110 Gnann H, Engelmann C, Skopp G et al. Identification of 48 homologues of phosphatidylethanol in blood by LC-ESI-MS/MS. Anal Bioanal Chem 2010; 396: 2415-2423
  • 111 Helander A, Zheng Y. Molecular species of the alcohol biomarker phosphatidylethanol in human blood measured by LC-MS. Clin Chem 2009; 55 (07) 1395-1405
  • 112 Wurst FM, Alexson S, Wolfersdorf M et al. Concentration of fatty acid ethyl esters in hair of alcoholics: Comparison to other biological state markers and self reported ethanol intake. Alcohol Alcohol 2004; 39: 33-38
  • 113 Hahn JA, Dobkin LM, Mayanja B et al. Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV-Positive patients in sub-Saharan Africa. Alcohol Clin Exp Res 2012; 36 (05) 854-862
  • 114 Aradóttir S, Seidl S, Wurst FM et al. Phosphatidylethanol in human organs and blood: a study on autopsy material and influences by storage conditions. Alcohol Clin Exp Res 2004; 28 (11) 1718-1723
  • 115 Varga A, Alling C. Formation of phosphatidylethanol in vitro in red blood cells from healthy volunteers and chronic alcoholics. J Lab Clin Med 2002; 140 (02) 79-83
  • 116 Babenko NA, Kharchenko VS. Ceramides inhibit phospholipase d-dependent insulin signaling in liver cells of old rats. Biochemistry 2012; 77: 180-186
  • 117 Nalesso A, Viel G, Cecchetto G et al. Quantitative profiling of phosphatidylethanol molecular species in human blood by liquid chromatography high resolution mass spectrometry. J Chromatogr A 2011; 1218 (46) 8423-8431
  • 118 Sampson PD, Streissguth AP, Bookstein FL et al. Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology 1997; 56 (05) 317-326
  • 119 Walsham NE, Sherwood RA. Ethyl glucuronide. Ann Clin Biochem 2012; 49 (02) 110-117
  • 120 Stade B, Ali A, Bennett D et al. The burden of prenatal exposure to alcohol: revised measurement of cost. Can J Clin Pharmacol 2009; 16 (01) e91-e102
  • 121 Vagnarelli F, Palmi I, García-Algar O et al. A survey of Italian and Spanish neonatologists and paediatricians regarding awareness of the diagnosis of FAS and FASD and maternal ethanol use during pregnancy. BMC Pediatr 2011; 11: 51
  • 122 Joya X, Friguls B, Ortigosa S et al. Determination of maternal-fetal biomarkers of prenatal exposure to ethanol: A review. J Pharm Biomed Anal 2012; 69: 209-222
  • 123 Bianchi V, Ivaldi A, Raspagni A et al. Pregnancy and variations of carbohydrate-deficient transferrin levels measured by the candidate reference HPLC method. Alcohol Alcohol 2011; 46 (02) 123-127
  • 124 Kenan N, Larsson A, Axelsson O et al. Changes in transferrin glycosylation during pregnancy may lead to false-positive carbohydrate-deficient transferrin (CDT) results in testing for riskful alcohol consumption. Clin Chim Acta 2011; 412 (01) 129-133
  • 125 Pichini S, Marchei E, Vagnarelli F et al. Assessment of prenatal exposure to ethanol by meconium analysis: results of an Italian multicenter study. Alcohol Clin Exp Res 2012; 36 (03) 417-424
  • 126 Zelner I, Hutson JR, Kapur BM et al. False-Positive Meconium Test Results for Fatty Acid Ethyl Esters Secondary to Delayed Sample Collection. Alcohol Clin Exp Res 2012; 36 (09) 1497-1506
  • 127 Morini L, Zucchella A, Polettini A et al. Effect of bleaching on ethyl glucuronide in hair: an in vitro experiment. Forensic Sci Int 2010; 198: 23-27
  • 128 Pragst F, Balikova MW. State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta 2006; 370: 17-49
  • 129 Morini L, Politi L, Polettini A. Ethyl glucuronide in hair. A sensitive and specific marker of chronic heavy drinking. Addiction 2009; 104: 915-920
  • 130 Auwärter V, Kiessling B, Pragst F. Squalene in hair- a natural reference substance for the improved interpretation of fatty acid ethyl ester concentrations with respect to alcohol misuse. Forensic Sci In 2004; 145: 149-159
  • 131 Kharbouche H, Steiner N, Morelato M et al. Influence of ethanol dose and pigmentation on the incorporation of ethyl glucuronide into rat hair. Alcohol 2010; 44 (06) 507-514
  • 132 Kintz P. Consensus of the Society of Hair Testing on hair testing for chronic excessive alcohol consumption. Forensic Sci Int 2009; 196: 2
  • 133 Society of Hair Testing. Consensus of the Society of Hair Testing on hair testing for chronic excessive alcohol consumption. 2009 ( http://soht.org/pdf/Consensus_EtG_2009.pdf Zugriff am 22.7.2012)
  • 134 Kronstrand R, Brinkhagen L, Nyström FH. Ethyl glucuronide in human hair after daily consumption of 16 or 32g of ethanol for 3 months. Forensic Sci Int 2012; 215 (01) 51-55
  • 135 Kerekes I, Yegles M, Grimm U. Ethyl glucuronide determination: head hair versus non-head hair. Alcohol Alcohol 2009; 44 (01) 62-66
  • 136 Sporkert F, Kharbouche H, Augsburger MP et al. Positive EtG findings in hair as a result of a cosmetic treatment. Forensic Sci Int 2012; 218 (01) 97-100
  • 137 Hartwig S, Auwärter V, Pragst F. Effect of hair care and hair cosmetics on the concentrations of fatty acid ethyl esters in hair as markers of chronically elevated alcohol consumption. Forensic Sci Int 2003; 131: 90-97
  • 138 Morini L, Groppi A, Marchei E et al. Population Baseline of Meconium Ethyl Glucuronide and Ethyl Sulfate Concentrations in Newborns of Nondrinking Women in 2 Mediterranean Cohorts. Ther Drug Monit 2010; [Epub ahead of print]
  • 139 Kulaga V, Velazquez-Armenta Y, Aleksa K et al. The effect of hair pigment on the incorporation of fatty acid ethyl esters (FSEE). Alcohol Alcohol 2009; 44: 287-292
  • 140 Appenzeller BM, Schuman M, Yegles M et al. Ethyl glucuronide concentration in hair is not influenced by pigmentation. Alcohol Alcohol 2007; 42: 326-327
  • 141 Pragst F, Rothe M, Moench B et al. Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages. Forensic Sci Int 2010; 196: 101-110
  • 142 Liniger B, Nguyen A, Friedrich-Koch A et al. Abstinence monitoring of suspected drinking drivers: ethyl glucuronide in hair versus CDT. Traffic Inj Prev 2010; 11: 123-126
  • 143 Arndt T, Gierten B, Güssregen B et al. False-positive ethyl glucuronide immunoassay screening associated with chloral hydrate medication as confirmed by LC-MS/MS and self-medication. Forensic Sci Int 2009; 184 (01) e27-e29
  • 144 Halter CC, Laengin A, Al-Ahmad A et al. Assessment of the stability of the ethanol metabolite ethyl sulfate in standardised degradation tests. Forensic Sci Int 2009; 186 (01) 52-55
  • 145 Aradóttir S, Seidl S, Wurst FM et al. Phosphatidylethanol in human organs and blood: a study on autopsy material and influences by storage conditions. Alcohol Clin Exp Res 2004; 28 (11) 1718-1723