Abstract
Fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) were determined in 602 meconium samples in a maternal health evaluation study for detection of gestational alcohol consumption. A validated headspace solid phase microextraction method in combination with GC-MS was used for FAEE and the cumulative concentration of ethyl palmitate, ethyl linoleate, ethyl oleate, and ethyl stearate with a cut-off of 500 ng/g was applied for interpretation. A new and simple method was developed and validated for quantification of EtG from 10–20 mg meconium with D 5-EtG as internal standard consisting of 30 min. extraction with methanol/water (1:1, v/v), evaporation of methanol, filtration of the aqueous solution through a cellulose filter and injection into LC-MS-MS. The limits of detection and quantification for EtG were 10 and 30 ng/g, the recovery 86.6 to 106.4% and the standard deviation of the concentrations ranged from 13% at 37 ng/g to 5% at 46,700 ng/g (N = 6). FAEE above the cut-off were found in 43 cases (7.1%) with cumulative concentrations between 507 and 22,580 ng/g and with one outlier of about 150,000 ng/g (EtG not detected). EtG was detected in 97 cases (16.3%) and concentrations between LOD and 10,200 ng/g with another outlier of 82,000 ng/g (FAEE 10,500 ng/g). Optimal agreement between the two markers was obtained with a cut-off for EtG of 274 ng/g and 547 cases with both FAEE- and EtG-negative, 33 cases with both FAEE- and EtG-positive, nine cases with FAEE-positive and EtG-negative, and seven cases with FAEE-negative and EtG-positive. Differences in physical, chemical, and biochemical properties and in the pharmacokinetic behavior are discussed as reasons for the deviating cases. In none of the 602 cases, serious alcohol consumption was reported by the mothers and no evidence for gestational ethanol exposure was observed in the medical investigation of the newborns. It is concluded that the combined use of FAEE and EtG in meconium as markers for fetal alcohol exposure essentially increases the accuracy of the interpretation and helps to avoid false positive and false-negative results.
Similar content being viewed by others
References
Mukherjee RAS, Hollins S, Turk J (2006) J Royal Soc Med 99:298–302
Manning MA, Hoyme HE (2007) Neurosci Behav Rev 31:230–238
Bearer CF, Lee S, Salvator AE, Minnes S, Swick A, Yamashita T, Singer LT (1999) Alcohol Clin Exp Res 23:487–493
Bearer CF, Jacobson JL, Jacobson SW, Barr D, Croxford J, Molteno CD, Viljoen DL, Marais AS, Chiodo LM, Cwik AS (2003) J Pediatr 143:463–469
Bearer CF, Santiago LM, O'Riordan MA, Buck K, Lee SC, Singer LT (2005) J Pediatr 146:824–830
Peterson J, Kirchner HL, Xue W, Minnes S, Singer LT, Bearer CF (2008) J Pediatr 152:788–792
Klein J, Karaskow T, Koren G (1999) Ther Drug Monit 21:644–646
Chan D, Bar-Oz B, Pellerin B, Paciorek C, Klein J, Kapur B, Farine D, Koren G (2003) Ther Drug Monit 25:271–278
Chan D, Caprara D, Blanchette P, Klein J, Koren G (2004) Clin Biochem 37:429–438
Chan D, Klein J, Karaskov T, Koren G (2004) Ther Drug Monit 26:474–481
Caprara DL, Nash K, Greenbaum R, Rovet J, Koren G (2007) Neurosci Behav Rev 31:354–360
Gareri J, Lynn H, Handley M, Rao C, Koren G (2008) Ther Drug Monit 30:239–245
Hutson JR, Aleksa K, Pragst F, Koren G (2009) J Chromatogr B Analyt Technol Biomed Life Sci 877:8–12
Zelner I, Koren G (2009) Ther Drug Monit 31:170–172
Moore CM, Lewis D (2001) Clin Chim Acta 312:235–237
Moore C, Jones J, Lewis D, Buchi K (2003) Clin Chem 49:133–136
Derauf C, Katz AR, Easa D (2003) Am J Epidemiol 158:705–709
Ostrea EM Jr, Hernandez JD, Bielawski DM, Kan JM, Leonardo GM, Abela MB, Church MW, Hannigan JH, Janisse JJ, Ager JW, Sokol RJ (2006) Alcohol Clin Exp Res 30:1152–1159
Burd L, Hofer R (2008) Birth Defects Res A Clin Mol Teratol 82:487–493
Garcia-Algar O, Kulaga V, Gareri J, Koren G, Vall O, Zuccaro P, Pacifici R, Pichini S (2008) Ther Drug Monit 30:249–254
Pichini S, Pellegrini M, Gareri J, Koren G, Garcia-Algar O, Vall O, Vagnarelli F, Zuccaro P, Marchei E (2008) Pharm Biomed Anal 48:927–933
Chan D, Knie B, Koren G (2003) Placenta 24:A41
Morini L, Marchei E, Pellegrini M, Groppi A, Stramesi C, Vagnarelli F, Garcia-Algar O, Pacifici R, Pichini S (2008) Ther Drug Monit 30:725–732
Pichini S, Morini L, Marchei E, Palmi I, Rotolo MC, Vagnarelli F, Garcia-Algar O, Vall O, Zuccaro P (2009) Can J Clin Pharmacol 16:e370–e375
Reulbach U, Bleich S, Knörr J, Burger P, Fasching PA, Kornhuber J, Beckmann MW, Goecke TW (2009) Fortschr Neurol Psychiatr 77:708–713
Pragst F, Auwaerter V, Sporkert F, Spiegel K (2001) Forensic Sci Int 121:76–88
Pragst F, Rothe M, Moench B, Hastedt M, Herre S, Simmert D (2010) Forensic Sci Int. doi:10.1016/j.forsciint.2009.12.028
Mierswa I, Wurst M, Klinkenberg R, Scholz M, Euler T (2006) Proceedings of the 12th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining (KDD-06)
Droenner P, Schmitt G, Aderjan R, Zimmer H (2002) Forensic Sci Int 126:24–29
Høiseth G, Bernard JP, Karinen R, Johnsen L, Helander A, Christophersen AS, Mørland J (2007) Forensic Sci Int 172:119–124
Høiseth G, Morini L, Polettini A, Christophersen A, Mørland J (2009) Forensic Sci Int 188:52–56
Halter CC, Dresen S, Auwaerter V, Wurst FM, Weinmann W (2008) Int J Legal Med 122:123–128
Bergström J, Helander A, Jones AW (2003) Forensic Sci Int 133:86–94
Gerdin E, Gabrielsson J, Lindberg B, Rane A (1990) Pharmacol Toxicol 66:815–819
Gerdin E, Rane A, Lindberg B (1990) J Perinat Med 18:305–312
Garland M, Abildskov KM, Taylor S, Benzeroual K, Caspersen CS, Arroyo SE, Kiu TW, Reznik B, Weldy P, Daniel SS, Stark RI (2006) Drug Metabol Dispos 34:636–646
De Giovanni N, Donadio G, Chiarotti M (2008) J Anal Toxicol 32:156–159
Kitchens JM (1994) J Am Med Assoc 272:1782–1787
Pragst F, Yegles M (2008) Ther Drug Monit 30:255–263
Author information
Authors and Affiliations
Corresponding author
Additional information
This work is dedicated to Professor Dr. Hans Helmut Kornhuber who passed away on October 30, 2009.
Abdulsallam Bakdash and Pascal Burger contributed equally to this work.
Rights and permissions
About this article
Cite this article
Bakdash, A., Burger, P., Goecke, T.W. et al. Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium from newborns for detection of alcohol abuse in a maternal health evaluation study. Anal Bioanal Chem 396, 2469–2477 (2010). https://doi.org/10.1007/s00216-010-3474-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-010-3474-5