Skip to main content

Advertisement

SpringerLink
Log in

Determination of direct alcohol markers: a review

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Alcohol is the most popular legal drug used in our society today, and its consumption by pregnant women remains an important public health problem. Gestational alcohol consumption can result in a continuum of adverse fetal outcomes known as fetal alcohol spectrum disorder (FASD). Effective strategies are needed to prevent the increasing adoption of risky drinking behaviors. Because ethanol itself is only measurable for a few hours after ethanol intake in conventional matrices including blood, urine, and sweat, these matrices are only useful to detect recent ethanol exposure. Since approximately early 2000, the non-oxidative ethanol metabolites have received increasing attention because of their specificity and, in some cases, wide time window of detection in non-conventional matrices including hair and meconium. In the attempt to update analytical methods for the determination of non-oxidative markers of alcohol, the objective of this study is to review published studies that measure fatty-acid ethyl esters (FAEE), ethyl glucuronide (EtG), and phosphatidylethanol (PEth) in alternative biological matrices, focusing on the extraction and detection methods and full analytical conditions used.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Parés A, Caballería J (2002) Patología orgánica. Adicciones 14(1):155–173

    Google Scholar 

  2. Betancourt A, Cuevas B, Terrado S, Valls M (2000) Marcadores biológicos en alcohólicos abstinentes. Adicciones 12(1):137–143

    Google Scholar 

  3. Maenhout M, Delanghe J (2013) Non-oxidative ethanol metabolites as a measure of alcohol intake. Clin Chim Acta 415:322–329

    CAS  Google Scholar 

  4. Jurado C (2009) Marcadores del consume de alcohol en muestras de pelo. Cuad Med Forense 15(58):265–278

    Google Scholar 

  5. Peterson K (2005) Biomarkers for alcohol use and abuse. A summary. Alcohol Res Health 28(1):30–37

    Google Scholar 

  6. Pragst F, Spiegel K, Sporkert F, Bohnenkamp M (2000) Are there possibilities for the detection of chronically elevated alcohol consumption by hair analysis? A report about the state of investigation. Forensic Sci Int 107(1–3):201–223

    CAS  Google Scholar 

  7. Yegles M, Labarthe A, Auwärter V, Hartwig S, Vater H, Wennig R, Pragst F (2004) Comparison of ethyl glucuronide and fatty acid ethyl esters concentration in hair of alcoholics, social drinkers and teetotallers. Forensic Sci Int 145(2–3):167–173

    CAS  Google Scholar 

  8. Pragst F, Rothe M, Moench B, Hastedt M, Herre S, Simmert D (2010) Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: Interpretation and advantages. Forensic Sci Int 196:101–110

    CAS  Google Scholar 

  9. Agius R, Ferreira L, Yegles M (2012) Can ethyl glucuronide in hair be determined only in 3 cm hair strands? Forensic Sci Int 218:3–9

    CAS  Google Scholar 

  10. Schräder J, Rothe M, Pragst F (2012) Ethyl glucuronide concentrations in beard hair after a single alcohol dose: evidence for incorporation in hair root. Int J Legal Med 126:791–799

    Google Scholar 

  11. Rainio J, De Giorgio F, Bortolotti F, Tagliaro F (2008) Objective post-mortem diagnosis of chronic alcohol abuse. A review of studies on new markers. Legal Med 10(5):229–235

    CAS  Google Scholar 

  12. Pianta A, Liniger B, Baumgartner R (2013) Ethyl glucuronide in scalp and non-head hair: an intra-individual comparison. Alcohol Alcohol 48(3):295–302

  13. Kharbouch H, Steiner N, Morelato M, Staub C, Boutrel B, Mangin P, Sporkert F, Augsburger M (2010) Influence of ethanol dose and pigmentation on the incorporation of ethyl glucuronide into rat hair. Alcohol 44(6):507–514

    Google Scholar 

  14. Auwärter V, Sporkert F, Hartwig S, Pragst F, Vater H, Diefenbacher A (2001) Fatty acid ethyl ester in hair as markers of alcohol consumption. Segmental hair analysis of alcoholics, social drinkers and teetotallers. Clin Chem 47(12):2114–2123

    Google Scholar 

  15. Musshoft F (2002) Chromatographic methods for the determination of markers of chronic and acute alcohol consumption. J Chromatogr B 781:457–480

    Google Scholar 

  16. Hartwig S, Auwärter V, Pragst F (2003) Fatty acid ethyl esters in scalp, pubic, axillary, beard and body hair as markers for alcohol misuse. Alcohol Alcohol 38(2):163–167

    CAS  Google Scholar 

  17. Wurst F, Alexson S, Wolfersdorf M, Bechtel G, Forster S, Alling C, Aradóttir S, Jachau K, Pragst F (2004) Concentration of fatty acid ethyl esters in hair of alcoholics: comparison to other biological state markers and self reported ethanol intake. Alcohol Alcohol 39(1):33–38

    CAS  Google Scholar 

  18. Auwärter V, Kiebling B, Pragst F (2004) Squalene in hair-a natural reference substance for the improved interpretation of fatty acid ethyl ester concentrations with respect to alcohol misuse. Forensic Sci Int 145:149–159

    Google Scholar 

  19. Sübe S, Selavka C, Mieczkowski T, Pragst F (2010) Fatty acid ethyl ester concentrations in hair and self-reported alcohol consumption in 644 cases from different origin. Forensic Sic Int 196:111–117

    Google Scholar 

  20. Albermann M, Musshoff F, Madea B (2011) Comparison of ethyl glucuronide and fatty acid ethyl esters concentration in hair for testing abstinence. Anal Bioanal Chem 400(1):175–181

    CAS  Google Scholar 

  21. Suesse S, Pragst F, Mieczkowski T, Selavka M, Elian A, Sachs H, Hastedt M, Rothe M, Campbell J (2012) Practical experiences in application of hair fatty acid ethyl esters and ethyl glucuronide for detection of chronic alcohol abuse in forensic cases. Forensic Sci Int 218(1–3):82–91

    CAS  Google Scholar 

  22. Kintz P, Villain M, Vallet E, Etter M, Salquebre G, Cirimele V (2008) Ethyl glucuronide:unusual distribution between head hair and pubic hair. Forensic Sci Int 176:87–90

    CAS  Google Scholar 

  23. Kerekes I, Yegles M, Grimm U, Wennig R (2009) Ethyl glucuronide determination. Head hair versus non-head hair. Alcohol Alcohol 44(1):62–66

    CAS  Google Scholar 

  24. Politi L, Morini L, Leone F, Polettini A (2006) Ethyl glucuronide in hair: is it a reliable maker of chronic high levels of alcohol consumption? Addiction 101:1408–1412

    Google Scholar 

  25. Cabarcos P, Álvarez I, Bermejo AM, Tabernero MJ, López P, Fernández P (2009) Analysis of fatty acid ethyl esters in hair by headspace solid-phase microextraction and gas chromatography-mass spectrometry. Anal Lett 42:2962–2977

    CAS  Google Scholar 

  26. Pragst F, Auwärter V, Sporkert F, Spiegel K (2001) Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid phase microextraction and gas chromatography-mass spectrometry. Forensic Sci Int 121:76–88

    CAS  Google Scholar 

  27. Mac E, Pacis M, García G, Ostrea EM (1994) A marker of fetal exposure to alcohol by meconium analysis. Pediatr Res 35:288A

    Google Scholar 

  28. Klein J, Karaskov T, Gideon K (1999) A novel biologic marker for heavy in utero ethanol exposure. A case report. Ther Drug Monit 21(6):644

    CAS  Google Scholar 

  29. Bearer C, Lee S, Salvator A, Minnes S, Swick A, Yamashita T, Singer L (1999) Ethyl linoleate in meconium. A biomarker for prenatal ethanol exposure. Alcohol Clin Exp Res 23(3):487–493

    CAS  Google Scholar 

  30. Cabarcos P, Tabernero MJ, Álvarez I, Miguez M, Fernández P, Bermejo AM (2012) A new method for quantifying prenatal exposure to ethanol by microwave-assisted extraction of meconium followed by gas chromatography-mass spectrometry. Anal Bioanal Chem 404:147–155

    CAS  Google Scholar 

  31. Joya X, Friguls B, Ortigosa S, Papaseit E, Martínez SE, Manich A (2012) Determination of maternal fetal biomarkers of prenatal exposure to ethanol. A review. J Pharm Biomed Anal 69:209–222

    CAS  Google Scholar 

  32. Chan D, Knie B, Boskovic R, Koren G (2004) Placental handling of fatty acid ethyl esters. Perfusion and subcellular studies. J Pharmacol Exp Ther 310(1):75–82

    CAS  Google Scholar 

  33. Caprara D, Klein J, Koren G (2005) Baseline measures of fatty acid ethyl esters in hair of neonates born to abstaining or mild social drinking mothers. Ther Drug Monit 27(6):811–815

    CAS  Google Scholar 

  34. Kulaga V, Velazquez-Armenta Y, Aleksa K, Vergee Z, Koren G (2009) The effect of hair pigment on the incorporation of fatty acid ethyl esters. Alcohol Alcohol 44(3):287–292

    CAS  Google Scholar 

  35. Consensus of the Society of Hair Testing (SoHT). Use of alcohol markers in hair for abstinence assessment 2012 http://www.soht.org/images/pdf/Use%20of%20Alcohol%20Markers%20in%20Hair%20for%20Abstinence%20Assessment%202012.pdf

  36. Kintz P (2010) Consensus of the Society of Hair Testing on hair testing for chronic excessive alcohol consumption 2009. Forensic Sci Int 196(1–3):2

  37. Hastedt M, Bossers L, Krumbiegel F, Herre S, Hartwig S (2013) Fatty acid ethyl esters in hair as alcohol markers: estimating a reliable cut-off point by evaluation of 1,057 autopsy cases. Forensic Sci Med Pathol 9(2):184–193

    CAS  Google Scholar 

  38. Moore C (2001) Fatty acid ethyl esters in meconium. Biomarkers for the detection of alcohol exposure in neonates. Clin Chim Acta 312:235–237

    CAS  Google Scholar 

  39. Moore C, Jones J, Lewis D, Buchi K (2003) Prevalence of fatty acid ethyl esters in meconium specimens. Clin Chem 49(1):133–136

    CAS  Google Scholar 

  40. Derauf C, Katz A, Easa D (2003) Agreement between maternal self-reported ethanol intake and tobacco use during pregnancy and meconium assays for fatty acid ethyl esters and cotinine. Am J Epidemiol 158(7):705–709

    Google Scholar 

  41. Hutson J, Rao C, Fulga N, Aleksa K, Koren G (2011) An improved method for rapidly quantifying fatty acid ethyl esters in meconium suitable for prenatal alcohol screening. Alcohol 45:193–199

    CAS  Google Scholar 

  42. Bakdash A, Burger P, Goecke T, Fasching P, Reulbach U, Bleich S, Hastedt M, Rothe M, Beckmann M, Pragst F, Kornhuber J (2010) Quantification of fatty acid ethyl esters and ethyl glucuronide in meconium from newborns for detection of alcohol abuse in a maternal health evaluation study. Anal Bioanal Chem 396:2469–2477

    CAS  Google Scholar 

  43. Bernhardt T, Cannistraro P, Bird D, Doyle K, Laposata M (1996) Purification of fatty acid ethyl esters by solid phase extraction and high performance liquid chromatography. J Chromatogr B 675:189–196

    CAS  Google Scholar 

  44. Hutson J, Aleksa K, Pragst F, Koren G (2009) Detection and quantification of fatty acid ethyl esters in meconium by headspace-solid phase microextraction and gas chromatography-mass spectrometry. J Chromatogr B 877:8–12

    CAS  Google Scholar 

  45. Illán F, Ojeda-Torres G, Díaz-Vázquez L, Rosario O (2011) Detection of fatty acid ethyl esters in skin surface lipids as biomarkers of ethanol consumption in alcoholics, social drinkers, Light drinkers and teetotallers using a methodology based on microwave-assisted extraction followed by solid phase microextraction and gas chromatography-mass spectrometry. J Anal Toxicol 35:232–237

    Google Scholar 

  46. Kinnunen PM, Lange LG (1984) Identification and quantification of fatty acid ethyl esters in biological specimens. Anal Biochem 140(2):567–576

    CAS  Google Scholar 

  47. Politi L, Zucchella A, Morini L, Stramesi C, Polettini A (2007) Markers of chronic alcohol use in hair: comparison of ethyl glucuronide and cocaethylene in cocaine users. Forensic Sci Int 172:23–27

    CAS  Google Scholar 

  48. Hartwig S, Auwärter V, Pragst F (2003) 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 131:90–97

    CAS  Google Scholar 

  49. Chan D, Bar-Oz B, Pellerin B, Paciorek C, Klein J, Kapur B, Farine D, Koren G (2003) Population baseline of meconium fatty acid ethyl esters among infants of nondrinking women in Jerusalem and Toronto. Ther Drug Monit 25:271–278

    CAS  Google Scholar 

  50. Bearer C, Jacobson J, Jacobson S, Barr D, Croxford J, Molteno C (2003) Validation of a new biomarker of fetal exposure to alcohol. J Pediatr 143:463–469

    CAS  Google Scholar 

  51. Chan D, Caprara D, Blanchette P, Klein J, Koren G (2004) Recent developments in meconium and hair testing methods for the confirmation of gestational exposures to alcohol and tobacco smoke. Clin Biochem 37:429–438

    CAS  Google Scholar 

  52. Kaphalia B, Cai P, Khan F, Okorodudu A, Ansari G (2004) Fatty acid ethyl esters: markers of alcohol abuse and alcoholism. Alcohol 34:151–158

    CAS  Google Scholar 

  53. Baricelli J, Barrera G, González J, Leal M, González D (2004) Niveles de ésteres etílicos de los ácidos grasos y perfil enzimático hepático en sangre cordonal de recién nacidos de madres consumidoras de alcohol. Salus 8(1):32

  54. Chan D, Caprara D, Blanchette P, Klein J, Koren G (2004) Recent developments in meconium and hair testing methods for the concentration of gestational exposures to alcohol and tobacco smoke. Clin Biochem 37:429–438

    CAS  Google Scholar 

  55. Caprara D, Brien JF, Iqbal U, Reynolds JN, Klein J (2005) A guinea pig model for the identification of in utero alcohol exposure using fatty acid ethyl esters in neonatal hair. Pediatr Res 58(6):1158–1163

    CAS  Google Scholar 

  56. Bearer C, Santiago LM, O’Riordan M, Buck K, Lee S, Singer L (2005) Fatty acid ethyl esters: quantitative biomarkers for maternal alcohol consumption. J Pediatr 146:824–830

    CAS  Google Scholar 

  57. Best C, Laposata M, Proios V, Szczepiorkowski Z (2006) Method to assess fatty acid ethyl ester binding to albumin. Alcohol Alcohol 41(3):240–246

    CAS  Google Scholar 

  58. Caprara D, Klein J, Koren G (2006) Diagnosis of fetal alcohol spectrum disorder (FASD): fatty acid ethyl esters and neonatal hair analysis. Ann Ist Super Sanitá 42(1):39–45

    CAS  Google Scholar 

  59. Kulaga V, Caprara D, Iqbal U, Kapure B, Klein J, Reynolds J, Brien J, Koren G (2006) Fatty acid ethyl esters: comparative accumulation in human and guinea pig hair as a biomarker for prenatal alcohol exposure. Alcohol Alcohol 41(5):534–539

    CAS  Google Scholar 

  60. Hutson J (2006) Meconium fatty acid ethyl esters and prediction of fetal alcohol effects. JFAS Int 4:15

    Google Scholar 

  61. Kulig C, Beresford T, Everson G (2006) Rapid, accurate and sensitive fatty acid ethyl ester determination by gas chromatography-mass spectrometry. J Lab Clin Med 147(3):133–138

    CAS  Google Scholar 

  62. Ostrea E, Hermández J, Bielawski D, Kan J, Leonardo G, Abela M, Church M, Hannigan J, Janisse J, Ager J, Sokol R (2006) Fatty acid ethyl esters in meconium. Are they biomarkers of fetal alcohol exposure and effect? Alcohol Clin Exp Res 30(7):1152–1159

    CAS  Google Scholar 

  63. Gareri J, Klein J, Koren G (2006) Drugs of abuse testing in meconium. Clin Chim Acta 366:101–111

    CAS  Google Scholar 

  64. Pragst F, Balikova MA (2006) State of the art in hair analysis for detection of drugs and alcohol abuse. Clin Chim Acta 370:17–49

    CAS  Google Scholar 

  65. Giovanni N, Donadio G, Chiarotti M (2007) The reliability of fatty acid ethyl esters as biological markers for the diagnosis of alcohol abuse. J Anal Toxicol 31:93–97

    Google Scholar 

  66. Caprara D, Nash K, Greenbaum R, Rovet J, Koren G (2007) Novel approaches to the diagnosis of fetal alcohol spectrum disorder. Neurosci Biobehav Rev 31:254–260

    CAS  Google Scholar 

  67. Hannuksela M, Liisanantti M, Nissinen A, Savolainen M (2007) Biochemical markers of alcoholism. Clin Chem Lab Med 45(8):953–961

    CAS  Google Scholar 

  68. Politi L, Leone F, Morini L, Polettini A (2007) Bioanalytical procedures for determination of conjugates or fatty acid ethyl esters of ethanol as markers of ethanol consumption: a review. Anal Biochem 368:1–16

    CAS  Google Scholar 

  69. Littner Y, Bearer C (2007) Detection of alcohol consumption during pregnancy. Current and future biomarkers. Neurosci Biobehav Rev 31:261–269

    CAS  Google Scholar 

  70. De Giovanni N, Donadio G, Chiarotti M (2008) Ethanol contamination leads to fatty acid ethyl esters in hair simples. J Anal Toxicol 32:156–159

    Google Scholar 

  71. Pichini S, Pellegrini M, Gareri J, Koren G, García-Algar O, Vall O, Vagnarelli F, Zuccaro P, Marchei E (2008) Liquid chromatography-tandem mass spectrometry for fatty acid ethyl esters in meconium. Assessment of prenatal exposure to alcohol in two European cohorts. J Pharm Biomed Anal 48:927–933

    CAS  Google Scholar 

  72. Algar O, Kulaga V, Gareri J, Koren G, Vall O, Zuccaro P, Pacifici R, Pichini S (2008) Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Ther Drug Monit 30(2):249–254

    Google Scholar 

  73. Peterson J, Kirchner L, Minnes S, Singer L, Bearer C (2008) Fatty acid ethyl esters in meconium are associated with poorer neurodevelopmental outcomes to two years of age. J Pedriatr 152(6):788–792

    CAS  Google Scholar 

  74. Gareri J, Lynn H, Handley M, Rao C, Koren G (2008) Prevalence of fetal ethanol exposure in a regional population based sample by meconium analysis of fatty acid ethyl esters. Ther Drug Monit 30(2):239–245

    CAS  Google Scholar 

  75. Burd L, Hofer R (2008) Biomarkers for detection of prenatal alcohol exposure. A critical review of fatty acid ethyl esters in meconium. Birth Defects Res (Part A) 82:487–493

    CAS  Google Scholar 

  76. Kulaga V, Pragst F, Koren G (2009) The fatty acid ethyl esters hair test: emerging technology for the diagnosis of fetal alcohol spectrum disorders (FASD). Ann Toxicol Anal 21(2):61–65

    CAS  Google Scholar 

  77. Kulaga V, Shor S, Koren G (2010) Correlation between drugs of abuse and alcohol by hair analysis: parents at risk for having children with fetal alcohol spectrum disorder. Alcohol 44:615–621

    CAS  Google Scholar 

  78. Kwak H, Kang Y, Han K, Moon J, Chung Y, Choi J, Han J, Kim M, Velázquez-Armenta Y, Nava-Ocampo A (2010) Quantitation of fatty acid ethyl esters in human meconium by an improved liquid chromatography/tandem mass spectrometry. J Chromatogr B 878:1871–1874

    CAS  Google Scholar 

  79. Hutson J, Magri R, Gareri J, Koren G (2010) The incidence of prenatal alcohol exposure in Montevideo Uruguay as determined by meconium analysis. Ther Drug Monit 32(3):311–317

    CAS  Google Scholar 

  80. Zelner I, Shor S, Gareri J, Lynn H, Roukema H, Lum L, Eisinga K, Nulman I, Koren G (2010) Universal screening for prenatal alcohol exposure. A progress report of a pilot study in the region of Grey Bruce, Ontario. Ther Drug Monit 32(3):305–310

    CAS  Google Scholar 

  81. Shor S, Nulman I, Kulaga V, Koren G (2010) Heavy in utero ethanol exposure is associated with the use of other drugs of abuse in a high-risk population. Alcohol 44:623–627

    CAS  Google Scholar 

  82. Goh Y, Hutson J, Lum L, Roukema H, Gareri J, Lynn H, Koren G (2010) Rates of fetal alcohol exposure among newborns in a high-risk obstetric unit. Alcohol 44:629–634

    Google Scholar 

  83. Roehsig M, Louzada de Paula D, Moura S, Albuquerque D, Yonamine M (2010) Determination of eight fatty acid ethyl esters in meconium samples by headspace solid-phase microextraction and gas chromatography-mass spectrometry. J Sep Sci 33:2115–2122

    CAS  Google Scholar 

  84. Politi L, Mari F, Furlanetto S, Del Bravo E, Bertol E (2011) Determination of fatty acid ethyl esters in hair by GC-MS and application in a population of cocaine users. J Pharm Biomed Anal 54:1192–1195

    CAS  Google Scholar 

  85. Gareri J, Appenzeller B, Walasek P (2011) Impact of hair care products on FAEE hair concentrations in substance abuse monitoring. Anal Bioanal Chem 400:183–188

    CAS  Google Scholar 

  86. Pichini S, Marchei E, Vagnarelli F, Li T, Raimondi F, Maffucci R, Sacher B, Bisceglia M, Rapisardi G, Elicio M, Biban P, Zuccaro P, Pacifici R, Pierantozzi A, Morini L (2012) Assessment of prenatal exposure to ethanol by meconium analysis. Results of an Italian multicenter study. Alcohol Clin Exp Res 36(3):417–424

    CAS  Google Scholar 

  87. Manich A, Velasco M, Joya X, García-Lara N, Pichini S, Vall O, García-Algar O (2012) Validez del cuestionario de consumo materno de alcohol para detectar la exposición prenatal. An Pediatr 76(6):324–328

    CAS  Google Scholar 

  88. Zelner I, Shor S, Lynn H, Roukema H, Lum L, Eisinga K, Koren G (2012) Clinical use of meconium fatty acid ethyl esters for identifying children at risk for alcohol-Related disabilities: the first reported case. J Popul Ther Clin Pharmacol 19(1):26–31

    Google Scholar 

  89. Zelner I, Hutson J, Kapur B, Feig D, Koren G (2012) False-positive meconium test results for fatty acid ethyl esters secondary to delayed sample collection. Alcohol Clin Exp Res 36(9):1497–1505

    CAS  Google Scholar 

  90. Zelner I, Shor S, Lynn H, Roukema H, Lum L, Eisinga K, Koren G (2012) Neonatal screening for prenatal alcohol exposure: assessment of voluntary maternal participation in an open meconium screening program. Alcohol 46:269–276

    CAS  Google Scholar 

  91. Zelner I, Kenna K, Brien J, Bocking A, Harding R, Walker D, Koren G (2013) Meconium fatty acid ethyl esters as biomarkers of fate gestational ethanol exposure and indicator of ethanol-induced multi-organ injury in fetal sheep. PLoS ONE 8(3):1–10

    Google Scholar 

  92. Morini L, Politi L, Acito S, Groppi A, Polettini A (2009) Comparison of ethyl glucuronide in hair with carbohydrate-deficient transferring in serum as markers of chronic high levels of alcohol consumption. Forensic Sci Int 188:140–143

    CAS  Google Scholar 

  93. Pragst F, Yegles M (2008) Determination of fatty acid ethyl esters and ethyl glucuronide in hair. A promising way for retrospective detection of alcohol abuse during pregnancy? Ther Drug Monit 30(2):255–263

    CAS  Google Scholar 

  94. Bendroth P, Kronstrand R, Helander A, Greby J, Stephanson N, Krantz P (2008) Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse. Forensic Sci Int 176:76–81

    CAS  Google Scholar 

  95. Appenzeller B, Agirman R, Neuberg P, Yegles M, Wennig R (2007) Segmental determination of ethyl glucuronide in hair: a pilot study. Forensic Sci Int 173(2–3):87–92

    CAS  Google Scholar 

  96. Hastedt M, Herre S, Pragst F, Rothe M, Hartwig S (2012) Workplace alcohol testing program by combined use of ethyl glucuronide and fatty acid ethyl esters in hair. Alcohol Alcohol 47(2):127–132

    CAS  Google Scholar 

  97. Bearer C (2001) Markers to detect drinking during pregnancy. Alcohol Res Health 25(3):210–218

    CAS  Google Scholar 

  98. Kamil IA, Smith JN, Williams RT (1952) A new aspect of ethanol metabolism: isolation of ethyl glucuronide. Biochem J 51:32–33

    Google Scholar 

  99. Tarcomnicu I, Van Nuijs A, Aerts K, De Doncher M, Covaci A, Neels H (2010) Ethyl glucuronide determination in meconium and hair by hydrophilic interaction liquid chromatography-tandem mass spectrometry. Forensic Sci Int 196:121–127

    CAS  Google Scholar 

  100. Lamoureux F, Gaulier JM, Sauvage FL, Mercerolle M, Vallejo C (2009) Determination of ethyl glucuronide in hair for heavy drinking detection using liquid-chromatography-tandem mass spectrometry following solid phase extraction. Anal Bioanal Chem 394:1895–1901

    CAS  Google Scholar 

  101. Álvarez I, Bermejo AM, Tabernero MJ, Fernández P, Cabarcos P, López P (2009) Microwave-assisted extraction: a simpler and master method for the determination of ethyl glucuronide in hair by gas chromatography-mass spectrometry. Anal Bioanal Chem 393:1345–1350

    Google Scholar 

  102. Kharbouche H, Sporkert F, Troxler S, Augsburger M, Mangin P, Christian C (2009) Development and validation of a gas chromatography-negative chemical ionization tandem mass spectrometry method for the determination of ethyl glucuronide in hair and its application to forensic toxicology. J Chromatogr B 877:2337–2343

    CAS  Google Scholar 

  103. Liniger B, Nguyen A, Friedrich-Koch A, Yegles M (2010) Abstinence monitoring of suspected drinking drivers: ethyl glucuronide in hair versus CDT. Traffic Inj Prev 11:123–126

    Google Scholar 

  104. Morini L, Marchei E, Vagnarelli F, García-Algar O, Groppi A, Mastrobattista L, Pichini S (2010) Ethyl glucuronide and ethyl sulphate in meconium and hair-potential biomarkers of intrauterine exposure to ethanol. Forensic Sci Int 196:74–77

    CAS  Google Scholar 

  105. Morini L, Marchei E, Tarani L, Trivelli M, Rapisardi G, Elicio MR, Ramis J, García-Algar O, Memo L, Pacifici R, Groppi A, Danesino P, Pichini S (2013) Ther Drug Monit 35(3):402–407

    CAS  Google Scholar 

  106. Pichini S, Morini L, Pacifini R, Tuyay J, Rodrigues W, Solimini R, García-Algar O, Ramis J, Moore C (2014) Development of a new immunoassay for the detection of ethyl glucuronide in meconium: validation with authentic specimens analyzed using LC-MS/MS. Preliminary results. Clin Chem Lab Med 52(8):1179–1185

    CAS  Google Scholar 

  107. Wurst F, Kempter C, Seidl S, Alt A (1999) Ethyl glucuronide, a marker of alcohol consumption and a relapse marker with clinical and forensic implications. Alcohol Alcohol 34(1):71–77

    CAS  Google Scholar 

  108. Skopp G, Schmitt G, Pötsch L, Drönner P, Aderjan R, Mattern R (2000) Ethyl glucuronide in human hair. Alcohol Alcohol 35(3):283–285

    CAS  Google Scholar 

  109. Alt A, Janda I, Seidl S, Wurst F (2000) Determination of ethyl glucuronide in hair samples. Alcohol Alcohol 35(3):313–314

    CAS  Google Scholar 

  110. Wurst F, Kempter C, Metzger J, Seidl S, Alt A (2000) Ethyl glucuronide: a marker of recent alcohol consumption with clinical and forensic implications. Alcohol 20:111–116

    CAS  Google Scholar 

  111. Seidl S, Wurst F, Alt A (2001) Ethyl glucuronide, a biological marker for recent alcohol consumption. Addict Biol 6:205–212

    CAS  Google Scholar 

  112. Janda I, Weinmann W, Kuehnle T (2002) Determination of ethyl glucuronide in human hair by SPE and LC-MS/MS. Forensic Sci Int 128:59–65

    CAS  Google Scholar 

  113. Wurst F, Metzger J (2002) The ethanol conjugate ethyl glucuronide is a useful marker of recent alcohol consumption. Alcohol Clin Exp Res 26(7):1114–1119

    CAS  Google Scholar 

  114. Weinmann W, Schaefer P, Thierauf A (2004) Confirmatory analysis of ethyl glucuronide in urine by liquid chromatography/electrospray ionization/tandem mass spectrometry according to forensic guidelines. J Am Soc Mass Spectrom 15:188–193

    CAS  Google Scholar 

  115. Jurado C, Soriano T, Giménez MP, Menéndez M (2004) Diagnosis of chronic alcohol consumption hair analysis for ethyl glucuronide. Forensic Sci Int 145:161–166

    CAS  Google Scholar 

  116. Skipper G, Weinmann W, Thierauf A, Schaefer P, Wiesbeck G, Allen J, Miller M, Wurst F (2004) Ethyl glucuronide: a biomarker to identify alcohol use by health professional recovering from substance use disorders. Alcohol Alcohol 39(5):445–449

    CAS  Google Scholar 

  117. Wurst F, Wiesbeck G, Metzger J, Weinmann W, Graf M (2004) On sensitivity, specificity and the influence of various parameters on ethyl glucuronide levels in urine results form the WHO/ISBRA study. Alcohol Clin Exp Res 28(8):1220–1228

    CAS  Google Scholar 

  118. Klys M, Scislowski M, Rojek S, Kolodziej J (2005) A fatal clomipramine intoxication case of a chronic alcoholic patient: application of post-mortem hair analysis method of clomipramine and ethyl glucuronide using LC-APCI/MS. Legal Med 7:319–325

    CAS  Google Scholar 

  119. Morini L, Politi L, Groppi A, Stramesi C, Polettini A (2006) Determination of ethyl glucuronide in hair samples by liquid chromatography/electrospray tandem mass spectrometry. J Mass Spectrom 41:34–42

    CAS  Google Scholar 

  120. Hoiseth G, Bernard J, Karinen R, Johnsen L, Helander A, Christophersen A, Morland J (2007) A pharmacokinetic study of ethyl glucuronide in blood and urine: application to forensic toxicology. Forensic Sci Int 172:119–124

    Google Scholar 

  121. Kugelberg F, Wayne JA (2007) Interpreting results of ethanol analysis in post-mortem specimens: a review of the literature. Forensic Sic Int 165:10–29

    CAS  Google Scholar 

  122. Wojcik M, Hawthorne J (2007) Sensitivity of commercial ethyl glucuronide testing in screening for alcohol abstinence. Alcohol Alcohol 42(4):317–320

    CAS  Google Scholar 

  123. Appenzeller B, Schuman M, Yegles M, Wennig R (2007) Ethyl glucuronide concentration in hair is not influence by pigmentation. Alcohol Alcohol 42(4):326–327

    CAS  Google Scholar 

  124. Jurado C (2007) Análisis de drogas de abuso en muestras de pelo. Diagnóstico del consumo crónico. Trastornos Adictivos 9(3):172–183

    Google Scholar 

  125. Niemelä O (2007) Biomarkers in alcoholism. Clin Chim Acta 377:39–49

    Google Scholar 

  126. Baranowski S, Serr A, Thierauf A, Weinmann W, Grobe M, Wurst F, Halter C (2008) In vitro study of bacterial degradation of ethyl glucuronide and ethyl sulphate. Int J Legal Med 122(5):389–393

    Google Scholar 

  127. Álvarez I, Bermejo AM, Cid P, Tabernero MJ, Fernández P, López P (2008) Microwave assisted extraction for the determination of ethyl glucuronide in urine by gas chromatography-mass spectrometry. J Appl Toxicol 28:773–778

    Google Scholar 

  128. Paul R, Kingston R, Tsanaclis L, Berry A, Guwy A (2008) Do drug users use less alcohol than non-drug users? A comparison of ethyl glucuronide concentrations in hair between the two groups in medico-legal cases. Forensic Sci Int 176:82–86

    CAS  Google Scholar 

  129. Klys M, Wozniak K, Rojek S, Rzepecka-Wozniak E, Kowalski P (2008) Ethanol related death of a child: an unusual case report. Forensic Sci Int 179:1–4

    Google Scholar 

  130. Politi L, Morini L, Mari F, Groppi A, Bertol E (2008) Ethyl glucuronide and ethyl sulphate in autopsy samples 27 years after death. Int J Legal Med 122:507–509

    Google Scholar 

  131. Bean P (2008) New finding with ethyl glucuronide testing in hair samples. Am Biotechnol Lab 26(7):20–21

    CAS  Google Scholar 

  132. Morini L, Marchei E, Pellegrini M, Groppi A, Stramesi C, Vagnarelli F, García-Algar O, Pacifini R, Pichini S (2008) Liquid chromatography with tandem mass spectrometry detection for the measurement of ethyl glucuronide and ethyl sulphate in meconium: new biomarkers of gestational ethanol exposure? Ther Drug Monit 30(6):725–732

    CAS  Google Scholar 

  133. Helander A, Böttcher M, Fehr C, Dahmen N, Beck O (2009) Detection times for urinary ethyl glucuronide and ethyl sulphate in heavy drinkers during alcohol detoxification. Alcohol Alcohol 44(1):55–61

    CAS  Google Scholar 

  134. Keten A, Tumer A, Balseven-Odabasi A (2009) Measurement of ethyl glucuronide in vitreous humor with liquid chromatography-mass spectrometry. Forensic Sci Int 193(1–3):101–105

    CAS  Google Scholar 

  135. Hoiseth G, Morini L, Polettini A, Christophersen A, Morland J (2009) Ethyl glucuronide in hair compared with traditional alcohol biomarkers. A pilot study of heavy drinkers referred to an alcohol detoxification unit. Alcohol Clin Exp Res 33(5):812–816

    Google Scholar 

  136. Morini L, Politi L, Polettini A (2009) Ethyl glucuronide in hair. A sensitive and specific marker of chronic heavy drinking. Addiction 104:915–920

    Google Scholar 

  137. Pichini S, Morini L, Marchei E, Palmi I, Rotolo M, Vagnarelli F, García-Algar O, Vall O, Zuccaro P (2009) Ethyl glucuronide and ethyl sulfate in meconium to assess gestational ethanol exposure: preliminary results in two mediterranean cohorts. Can J Clin Pharmacol 16(2):370–375

    Google Scholar 

  138. Concheiro M, Cruz A, Mon M, De Castro A, Quintela O, Lorenzo A, López-Rivadulla M (2009) Ethyl glucuronide determination in urine and hair from alcohol withdrawal patients. J Anal Toxicol 33(3):155–161

    CAS  Google Scholar 

  139. Albermann M, Musshoff F, Madea B (2010) A fully validated high-performance liquid chromatography-tandem mass spectrometry method for the determination of ethyl glucuronide in hair for the proof of strict alcohol abstinence. Anal Bioanal Chem 396:2441–2447

    CAS  Google Scholar 

  140. Agius R, Nadulski T, Kahl H, Schräder J, Dufaux B, Yegles M, Pragst F (2010) Validation of a headspace solid-phase microextraction for the determination of ethyl glucuronide in hair according to forensic guidelines. Forensic Sci Int 196:3–9

    CAS  Google Scholar 

  141. Morini L, Groppi A, Marchei E, Vagnarelli F, García-Algar O, Zuccaro P, Pichini S (2010) Population baseline of meconium ethyl glucuronide and ethyl sulfate concentrations in newborns of nondrinking women in 2 mediterranean cohorts. Ther Drug Monit 32(3):359–363

    CAS  Google Scholar 

  142. Morini L, Falcón M, Pichini S, García-Algar O, Danesino P, Groppi A, Luna A (2011) Ethyl glucuronide and ethyl sulfate in placental and fetal tissues by liquid chromatography coupled with tandem mass spectrometry. Anal Biochem 418:30–36

    CAS  Google Scholar 

  143. Tavakoli H, Hull M, Okasinski M (2011) Review of current clinical biomarkers for the detection of alcohol dependence. Innov Clin Neurosci 8(3):26–33

    Google Scholar 

  144. Agius R, Nadulski T, Kahl HG, Dufaux B (2012) Ethyl glucuronide in hair. A highly effective test for the monitoring of alcohol consumption. Forensic Sci Int 218:10–14

    CAS  Google Scholar 

  145. Lees R, Kingston R, Williams T, Henderson G, Hughes A, Hickman M (2012) Comparison of ethyl glucuronide in hair with self-reported alcohol consumption. Alcohol Alcohol 47(3):267–272

    CAS  Google Scholar 

  146. Malkowska A, Szutowski M, Dyr W (2012) Deposition of ethyl glucuronide in WHP rat hair after chronic ethanol intake. Pharmacol Rep 64:586–593

    CAS  Google Scholar 

  147. Kharbouche H, Faouzi M, Sánchez N, Daeppen JB, Augsburger M, Mangin P, Staub C, Sporkert F (2012) Diagnostic performance of ethyl glucuronide in hair for the investigation of alcohol drinking behaviour: a comparison with traditional biomarkers. Int J Legal Med 126:243–250

    Google Scholar 

  148. Pragst F (2012) Interpretation problems in a forensic case of abstinence determination using alcohol markers in hair. Forensic Sci Int 217:4–7

    Google Scholar 

  149. Kronstrand R, Brinkhagen L, Nyström F (2012) Ethyl glucuronide in human hair after daily consumption of 16 or 32 g of ethanol for 3 months. Forensic Sci Int 215:51–55

    CAS  Google Scholar 

  150. Albermann M, Musshoff F, Aengenheister L, Madea B (2012) 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 403:769–776

    CAS  Google Scholar 

  151. Sporkert F, Kharbouche H, Augsburger M, Klemm C, Baumgartner M (2012) Positive ethyl glucuronide findings in hair as a results of a cosmetic treatment. Forensic Sci Int 218:97–100

    CAS  Google Scholar 

  152. Ferreira L, Binz T, Yegles M (2012) The influence of ethanol containing cosmetics on ethyl glucuronide concentration in hair. Forensic Sci Int 218:123–125

    Google Scholar 

  153. Stewart S, Koch D, Willne I, Randall P, Reuben A (2013) Hair ethyl glucuronide is highly sensitive and specific for detecting moderate-to-heavy drinking in patients with liver disease. Alcohol Alcohol 48(1):83–87

    CAS  Google Scholar 

  154. Hoiseth G, Morini L, Ganss R, Nordal K, Morland J (2013) Higher levels of hair ethyl glucuronide in patients with decreased kidney function. Alcohol Clin Exp Res 37(1):14–16

    Google Scholar 

  155. Cabarcos P, Hassan H, Tabernero MJ, Scott K (2013) Analysis of ethyl glucuronide in hair samples by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). J Appl Toxicol 33(7):638–643

    CAS  Google Scholar 

  156. Viel G, Boscol-Berto R, Cecchetto G, Fais P, Nalesso A, Ferrara S (2012) Phosphatidylethanol in blood as a marker of chronic alcohol use: a systematic review and meta-analysis. Int J Mol Sci 13:14788–14812

    CAS  Google Scholar 

  157. Gunnarsson T, Karlsson A, Hansson P, Johnson G, Alling C, Odham G (1998) Determination of phosphatidylethanol in blood from alcoholic males using high-performance liquid chromatography and evaporative light scattering or electrospray mass spectrometric detection. J Chromatogr B 705:243–249

    CAS  Google Scholar 

  158. Changsuek Y, Han J (2000) Analysis of trimethylsilyl derivatization products of phosphatidylethanol by gas chromatography-mass spectrometry. Exp Mol Med 32(4):243–245

    Google Scholar 

  159. Hansson P, Varga A, Krantz P, Alling C (2001) Phosphatidylethanol in post-mortem blood as a marker of previous heavy drinking. Int J Legal Med 115:158–161

    CAS  Google Scholar 

  160. Varga A, Nilsson S (2002) Formation of phosphatidylethanol in vitro in red blood cells from healthy volunteers and chronic alcoholics. J Lab Clin Med 140(2):79–83

    CAS  Google Scholar 

  161. Aradottir S, Moller K, Alling C (2004) Phosphatidylethanol formation and degradation in human and rat blood. Alcohol Alcohol 39(1):8–13

    CAS  Google Scholar 

  162. Tolonen A, Lehto T, Hannuksela M, Savolainen M (2005) A method for determination of phosphatidylethanol from high density lipoproteins by reversed-phase HPLC with TOF-MS detection. Anal Biochem 341:83–88

    CAS  Google Scholar 

  163. Aradottir S, Olsson B (2005) Methodological modifications on quantification of phosphatidylethanol in blood from humans abusing alcohol, using high-performance liquid chromatography and evaporative light scattering detection. BCM Biochem 6(18):1–8

    Google Scholar 

  164. Aradottir S, Asanovska G, Gjerss S, Hansson P, Alling C (2006) Phosphatidylethanol concentrations in blood are correlated to reported alcohol intake in alcohol-dependent patients. Alcohol Alcohol 41(4):431–437

    CAS  Google Scholar 

  165. Hartmann S, Aradottir S, Graf M, Wiesbeck G, Lesch O, Ramskogler K, Wolfersdorf M, Alling C, Wurst F (2006) Phosphatidylethanol as a sensitive and specific biomarker-comparison with gamma-glutamyltranspeptidase, mean corpuscular volume and carbohydrate-deficient transferring. Addict Biol 12:81–84

    Google Scholar 

  166. Nissinen A, Mäkelä S, Vuoristo J, Liisanantti M, Hannuksela M, Hörkkö S, Savolainen M (2008) Immunological detection of in vitro formed phosphatidyletahnol- An alcohol biomarker with monoclonal antibodies. Alcohol Clin Exp Res 32(6):921–928

    CAS  Google Scholar 

  167. Kip M, Spies C, Neumann T, Nachbar Y, Alling C, Aradottir S, Weinmann W, Wurst F (2008) The usefulness of direct ethanol metabolites in assessing alcohol intake in nonintoxicated male patients in an emergency room setting. Alcohol Clin Exp Res 32(7):1284–1291

    Google Scholar 

  168. Varga A, Nilsson S (2008) Nonaqueous capillary electrophoresis for analysis of the ethanol consumption biomarker phosphatidylethanol. Electrophoresis 29:1667–1671

    CAS  Google Scholar 

  169. Gnann H, Weinmann W, Engelmann C, Wurst F, Skopp G, Winkler M, Thierauf A, Auwärter V, Dresen S, Bouzas N (2009) Selective detection of phosphatidylethanol homologues in blood as biomarkers for alcohol consumption by LC-ESI-MS/MS. J Mass Spectrom 44:1293–1299

    CAS  Google Scholar 

  170. Helander A, Zheng Y (2009) Molecular species of the alcohol biomarker phosphatidylethanol in human blood measured by LC-MS. Clin Chem 55(7):1395–1405

    CAS  Google Scholar 

  171. Comasco E, Nordquist N, Leppert J, Oreland L, Kronstrand R, Alling C, Nilsson K (2009) Adolescent alcohol consumption: biomarkers PEth and FAEE in relation to interview and questionnaire data. J Stud Alcohol Drugs 70(5):797–804

    Google Scholar 

  172. Wurst F, Thon N, Aradottir S, Hartmann S, Wiesbeck G, Lesch O, Skala K, Wolfersdorf M, Weinmann W, Alling C (2010) Addict Biol 15:88–95

    CAS  Google Scholar 

  173. Stewart S, Law T, Randall P, Newman R (2010) Phosphatidylethanol and alcohol consumption in reproductive age women. Alcohol Clin Exp Res 34(3):488–492

    CAS  Google Scholar 

  174. Gnann H, Enfelmann C, Skopp G, Winkler M, Auwärter V, Dresen S, Ferreirós N, Wurst F, Weinmann W (2010) Identification of 48 homologues of phosphatidylethanol in blood by LC-ESI-MS/MS. Anal Bioanal Chem 396:2415–2423

    CAS  Google Scholar 

  175. Nalesso A, Viel G, Cecchetto G, Mioni D, Pessa G, Favretto D, Ferrara S (2011) Quantitative profiling of phosphatidylethanol molecular species in human blood by liquid chromatography high resolution mass spectrometry. J Chromatogr A 1218:8423–8431

    CAS  Google Scholar 

  176. Zheng Y, Beck O, Helander A (2011) Method development for routine liquid chromatography-mass spectrometry measurement of the alcohol biomarker phosphatidylethanol in blood. Clin Chim Acta 412:1428–1435

    CAS  Google Scholar 

  177. Faller A, Richter B, Kluge M, Koenig P, Seitz H, Thierauf A, Gnann H, Winkler M, Mattern R, Skopp G (2011) LC-MS/MS analysis of phosphatidylethanol in dried blood spots versus conventional blood specimens. Anal Bioanal Chem 401:1163–1166

    CAS  Google Scholar 

  178. Isaksson A, Walther L, Hansson T, Andersson A, Alling C (2011) Phosphatidylethanol in blood (B-PEth): a marker for alcohol use and abuse. Drug Test Anal 3:195–200

    CAS  Google Scholar 

  179. Gnann H, Weinmann W, Thierauf A (2012) Formation of phosphatidyletanol and its subsequent elimination during an extensive drinking experiment over 5 days. Alcohol Clin Exp Res 36(9):1507–1510

    CAS  Google Scholar 

  180. Faller A, Richter B, Kluge M, Koenig P, Seitz H, Skopp G (2012) Stability of phosphatidylethanol species in spiked and authentic whole blood and matching dried blood spots. Int J Legal Med 127(3):603–610

    Google Scholar 

  181. Kwak H, Han J, Ahn H, Kim M, Ryu H, Kim M-Y, Chung D, Shin C, Velázquez-Armenta E, Nava-Ocampo A (2012) Blood levels of phosphatidylethanol in pregnant women reporting positive alcohol ingestion, measured by an improved LC-MS/MS analytical method. Clin Toxicol 50:886–891

    CAS  Google Scholar 

  182. Winkler M, Skopp G, Alt A, Miltner E, Jochum T, Daenhardt C, Sporkert F, Gnann H, Weinmann W, Thierauf A (2013) Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication. Int J Legal Med 127(4):761–768

    CAS  Google Scholar 

  183. Cabarcos P, Cocho JA, Moreda A, Míguez M, Tabernero MJ, Fernández P, Bermejo AM (2013) Application of dispersive liquid-liquid microextraction for the determination of phosphatidylethanol in blood by liquid chromatography tandem mass spectrometry. Talanta 111:189–195

    CAS  Google Scholar 

Download references

Conflict of interest

The authors have nothing to disclose

Author information

Authors and Affiliations

  1. Forensic Science Institute, Faculty of Medicine, University of Santiago de Compostela, C/San Francisco s/n, 15782, Santiago de Compostela, Spain

    Pamela Cabarcos, Iván Álvarez, María Jesús Tabernero & Ana María Bermejo

Authors
  1. Pamela Cabarcos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iván Álvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María Jesús Tabernero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana María Bermejo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana María Bermejo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cabarcos, P., Álvarez, I., Tabernero, M.J. et al. Determination of direct alcohol markers: a review. Anal Bioanal Chem 407, 4907–4925 (2015). https://doi.org/10.1007/s00216-015-8701-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-015-8701-7

Keywords

Search

Navigation