Skip to main content
SpringerLink
Log in

Endogenous gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

When interpreting gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens, a possible increase in GHB concentrations because of post-mortem generation must be considered. In this study, endogenous GHB concentrations in post-mortem biological fluids were investigated. Additionally, we review post-mortem GHB concentrations already published in the literature. Heart and peripheral blood samples, cerebrospinal fluid, urine, and vitreous humor were collected from 64 autopsies in subjects where the cause of death excluded GHB exposure. Sample analysis was carried out either on the day of autopsy or later after immediate freezing and storage at −20 °C. GHB concentrations in venous blood samples (n = 61) were <0.6–28.7 mg/L (mean 11.9 mg/L; median 10.6 mg/L), <0.6–65.3 mg/L (mean 15.2 mg/L; median 12.8 mg/L) in heart blood (n = 56), <0.6–25.1 mg/L (mean 6.0 mg/L; median 3.8 mg/L) in urine (n = 50), <0.6–39.0 mg/L (mean 9.6 mg/L; median 7.5 mg/L), in vitreous humor (n = 54), and <0.6–24.0 mg/L (mean 4.2 mg/L; median 3.2 mg/L) in cerebrospinal fluid (n = 52). There was no significant difference between GHB concentrations in cases where there were signs of beginning putrefaction at the time of autopsy (n = 9) and cases without obvious signs of putrefaction. In one case with advanced putrefaction, the GHB concentration in venous blood was 32.7 mg/L. In conclusion, for post-mortem venous blood, urine, and cerebrospinal fluid, an interpretative cut-off of 30 mg/L for GHB concentrations is suggested in cases where GHB analysis is conducted on the day of sample collection at autopsy or if samples have been stored at −20 °C immediately after collection.

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
Fig. 2

Similar content being viewed by others

References

  1. Abanades S, Farré M, Barral D, Torrens M, Closas N, Langohr K, Pastor A, De la Torre R (2007) Relative abuse liability of gamma-hydroxybutyric acid, flunitrazepam, and ethanol in club drug users. J Clin Psychopharmacol 17:625–638

    Article  CAS  Google Scholar 

  2. Abanades S, Farré M, Segura M, Pichini M, Pastor A, Pacifici R, Pellegrini M, de la Torre R (2007) Disposition of gamma-hydroxybutyric acid in conventional and nonconventional biologic fluids after single drug administration: issues in methodology and drug monitoring. Ther Drug Monit 29(1):64–70

  3. Miotto K, Darakjian J, Basch J, Murray S, Zogg J, Rawson R (2001) Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal. Am J Addict 10(3):232–241

    Article  CAS  PubMed  Google Scholar 

  4. Elliott S (2004) Nonfatal instances of intoxication with gamma-hydroxybutyrate in the United Kingdom. Ther Drug Monit 26(4):432–440

    Article  CAS  PubMed  Google Scholar 

  5. Couper FJ, Logan BK (2000) Determination of gamma-hydroxybutyrate (GHB) in biological specimens by gas chromatography-mass spectrometry. J Anal Toxicol 24:1–7

    Article  CAS  PubMed  Google Scholar 

  6. Sporer K, Chin R, Dyer J, Lamb R (2003) Gamma-hydroxybutyrate serum levels and clinical syndrome after severe overdose. Ann Emerg Med 42:3–8

    Article  PubMed  Google Scholar 

  7. Mason P, Kerns W (2002) Gamma hydroxybutyric acid (GHB) intoxication. Acad Emerg Med 9(7):730–739

    Article  PubMed  Google Scholar 

  8. Duer WC, Byers KL, Martin JV (2001) Application of a convenient extraction procedure to analyze gamma-hydroxybutyric acid in fatalities involving gamma-hydroxybutyric acid, gamma-butyrolactone, and 1,4-butanediol. J Anal Toxicol 25:576–582

    Article  CAS  PubMed  Google Scholar 

  9. Mazarr-Proo S, Kerrigan S (2005) Distribution of GHB in tissues and fluids following a fatal overdose. J Anal Toxicol 29:398–400

    Article  CAS  PubMed  Google Scholar 

  10. Kintz P, Villain M, Pélisser A-L, Cirimele V, Leonetti G (2005) Unusually high concentrations in a fatal GHB case. J Anal Toxicol 29:582–585

    Article  CAS  PubMed  Google Scholar 

  11. Kalasinsky K, Dixon M, Schmunk G, Kish S (2001) Blood, brain, and hair GHB concentrations following fatal ingestion. J Forensic Sci 46(3):728–730

    Article  CAS  PubMed  Google Scholar 

  12. Knudsen K, Jonsson U, Abrahamsson J (2010) Twenty-three deaths with γ-hydroxybutyrate overdose in Western Sweden between 2000 and 2007. Acta Anaesthesiol Scand 54(8):987–992

    Article  CAS  PubMed  Google Scholar 

  13. Zvosec D, Smith S, Porrata T, Strobl A, Dyer J (2011) Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and trauma. Am J Emerg Med 29(3):319–332

    Article  PubMed  Google Scholar 

  14. Kugelberg F, Holmgren A, Eklund A, Jones A (2010) Forensic toxicology findings in deaths involving gamma-hydroxybutyrate. Int J Legal Med 124(1):1–6

    Article  PubMed  Google Scholar 

  15. Lenz D, Rothschild M, Kroener L (2008) Intoxications due to ingestion of gamma-butyrolactone: organ distribution of gamma-hydroxybutyric acid and gamma-butyrolactone. Ther Drug Monit 30(6):755–761

    Article  PubMed  Google Scholar 

  16. Zvosec DL, Smith SW, McCutcheon R, Spillane J, Hall BJ, Peacock E (2001) Adverse events, including death, associated with the use of 1, 4-butanediol. N Engl J Med 344:87–94

    Article  CAS  PubMed  Google Scholar 

  17. ElSohly MA, Salamone SJ (1999) Prevalence of drug used in cases of alleged sexual assault. J Anal Toxicol 23:141–146

    Article  CAS  PubMed  Google Scholar 

  18. LeBeau MA, Andollo W, Hearn W, Baselt R, Cone E, Finkle B, Fraser D, Jenkins A, Mayer J, Negrusz A, Poklis A, Walls H, Raymon L, Robertson M, Saady J (1999) Recommendation for toxicological investigations of drug-facilitated sexual assaults. J Forensic Sci 44:227–230

    Article  CAS  PubMed  Google Scholar 

  19. Marinetti L, LeBeau M (2010) The use of GHB and analogs to facilitate sexual assault. Forensic Sci Rev 22:41

    CAS  PubMed  Google Scholar 

  20. Roth RH, Giarman NJ (1970) Natural occurrence of gamma-hydroxybutyrate in mammalian brain. Biochem Pharmacol 19:1087–1093

    Article  CAS  Google Scholar 

  21. Bessman S, Fishbein W (1963) Gamma-hydroxybutyrate, a normal brain metabolite. Nature 200:1207–1208

    Article  CAS  PubMed  Google Scholar 

  22. Elliott S (2003) Gamma hydroxybutyric acid (GHB) concentrations in humans and factors affecting endogenous production. Forensic Sci Int 133:9–16

    Article  CAS  PubMed  Google Scholar 

  23. Bosman IJ, Lusthof KJ (2003) Forensic cases involving the use of GHB in the Netherlands. Forensic Sci Int 133:17–21

    Article  CAS  PubMed  Google Scholar 

  24. Elian AA (2002) Determination of endogenous gamma-hydroxybutyric acid (GHB) levels in antemortem urine and blood. Forensic Sci Int 128:120–122

    Article  CAS  PubMed  Google Scholar 

  25. Kavanagh P, Kenny P, Feely J (2001) The urinary excretion of gamma-hydroxybutyric acid in man. J Pharm Pharmacol 53:399–402

    Article  CAS  PubMed  Google Scholar 

  26. Andresen H, Sprys N, Schmoldt A, Mueller A, Iwersen-Bergmann S (2010) Gamma-hydroxybutyrate in urine and serum: additional data supporting current cut-off recommendations. Forensic Sci Int 200:93–99

    Article  CAS  PubMed  Google Scholar 

  27. Fieler EL, Coleman DE, Baselt RC (1998) Gamma-hydroxybutyrate concentrations in pre- and postmortem blood and urine. Clin Chem 44:692–693

    Article  CAS  PubMed  Google Scholar 

  28. Kintz P, Villain M, Cirimele V, Ludes B (2004) GHB in postmortem toxicology. discrimination between endogenous production from exposure using multiple specimens. Forensic Sci Int 143:177–181

    Article  CAS  PubMed  Google Scholar 

  29. Elliott S (2001) The presence of gamma-hydroxybutyric acid (GHB) in postmortem biological fluids. J Anal Toxicol 25:152

    Article  CAS  Google Scholar 

  30. Moriya F, Hashimoto Y (2004) Endogenous gamma-hydroxybutyric acid levels in postmortem blood. Legal Med 6:47–51

    Article  CAS  PubMed  Google Scholar 

  31. Doherty J, Hattox S, Snead O, Roth R (1978) Identification of endogenous gamma-hydroxybutyrate in human and bovine brain and its regional distribution in human, guinea pig and rhesus monkey brain. J Pharmacol Exp Ther 207(1):130–139

    CAS  PubMed  Google Scholar 

  32. Or S, Liu C, Bearden L (1982) Studies on the relation of gamma-hydroxybutyric acid (GHB) to gamma-aminobutyric acid (GABA). Evidence that GABA is not the sole Source for GHB in Rat. Brain Biochem Pharmacol 31(23):3917–3923

    Article  PubMed  Google Scholar 

  33. Sakurada K, Kobayashi M, Iwase H, Yoshino M, Mukoyama H, Takatori T, Yoshida K (2002) Production of gamma-hydroxybutyric acid in postmortem liver increases with time after death. Toxicol Lett 129:207–217

    Article  CAS  PubMed  Google Scholar 

  34. Seiler N, Schmidt-Glenewinkel T, Sarhan S (1979) On the formation of gamma-aminobutyric acid from putrescine in brain. J Biochem 86:277–278

    CAS  PubMed  Google Scholar 

  35. Marinetti LJ, Isenschmid DS, Hepler BR, Kanluen S (2005) Analysis of GHB and 4-methyl-GHB in postmortem matrices after long-term storage. J Anal Toxicol 29:41–47

    Article  CAS  PubMed  Google Scholar 

  36. Petersen I, Tortzen C, Kristensen J, Pedersen D, Breindahl T (2013) Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide. J Anal Toxicol 37:291–297

    Article  CAS  PubMed  Google Scholar 

  37. Moriya F, Hashimoto Y (2005) Site-dependent production of gamma-hydroxybutyric acid in the early postmortem period. Forensic Sci Int 148:139–142

    Article  CAS  PubMed  Google Scholar 

  38. Elliott S (2004) Further evidence for the presence of GHB in postmortem biological fluid: implications for the interpretation of findings. J Anal Toxicol 28:20–26

    Article  CAS  PubMed  Google Scholar 

  39. Stephens B, Coleman D, Baselt R (1999) In vitro stability of endogenous gamma-hydroxybutyrate in postmortem blood. J Forensic Sci 44:231

    Article  CAS  PubMed  Google Scholar 

  40. Kerrigan S (2002) In vitro production of gamma-hydroxybutyrate in antemortem urine samples. J Anal Toxicol 26:571–574

    Article  CAS  PubMed  Google Scholar 

  41. Shah V, Midha K, Findlay J, Hill H, Hulse J, McGilveray I, McKay G, Miller K, Patnaik R, Powell M, Tonelli A, Viswanathan C, Yacobi A (2000) Bioanalytical method validation—a revisit with a decade of progress. Pharm Res 17(12):1551–1557

    Article  CAS  PubMed  Google Scholar 

  42. Paul L, Mußhoff F, Aebi B, Auwärter V, Krämer T, Peters F, Skopp G, Aderjan R, Herbold M, Schmitt G, Thieme D, Tönnes S, Andresen H, Becker J, J B, Briellmann T, Bussemas H, Erdmann F, Hanke M, Kreutzberg S, Krüger G, Schmitt G (2009) Richtlinie der GTFCh zur Qualitätssicherung bei forensisch-toxikologischen Untersuchungen (Guidelines for quality assurance in forensic-toxicological analyses). http://www.gtfch.org/cms/images/stories/files/GTFCh_Richtlinie_For-Tox_Version%201.pdf.

  43. Erdmann F, Zandt D, Auch J, Schütz H, Weiler G, Verhoff M (2006) Investigations concerning the threshold value between endogenous and exogenous GHB (liquid ecstasy). Arch Kriminol 217(5–6):129–136, German

    PubMed  Google Scholar 

  44. Anderson D, Kuwahara T (1997) Endogenous GHB concentrations in postmortem specimens. Presented at the California Association of Toxicologists Meeting, Las Vegas, NV

  45. Eklund A, Eriksson M (2000) GHB endogenous concentrations, abuse, traffic accidents and death. Poster presented at the International Association of Forensic Toxicologists Meeting, Helsinki, Finland

  46. Quattrocchi F, Sullivan L, Gray K (2001) Postmortem data review of gamma-hydroxybutyrate levels. Poster presented at the American Academy of Forensic Science Meeting, Seattle, WA

  47. Kalasinsky KS, Dixon MM, Schmunk GA, Kish SJ (2001) Blood, brain and hair GHB concentrations following fatal ingestion. J Forensic Sci 46(3):728–730

    Article  CAS  PubMed  Google Scholar 

  48. Fjeld B, Burns M, Karinen R, Larssen B, Smith-Kielland A, Vindenes V (2012) Long-term stability of GHB in post-mortem samples and samples from living persons, stored at -20 °C, using fluoride preservatives. Forensic Sci Int 222(1–3):47–51

    Article  CAS  PubMed  Google Scholar 

  49. Elliott S, Lowe P, Amanda S (2004) The possible influence of micro-organisms and putrefaction in the production of GHB in post-mortem biological fluid. Forensic Sci Int 139:183–190

    Article  CAS  PubMed  Google Scholar 

  50. Villain M, Cirimele V, Ludes B, Kintz P (2003) Ultra-rapid procedure to test for gamma-hydroxybutyric acid in blood and urine by gas chromatography-mass spectrometry. J Chromatogr 792:83–87

    CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Legal Medicine, Department of Toxicology, University Medical Center Hamburg—Eppendorf, Butenfeld 34, 22529, Hamburg, Germany

    Hilke Andresen-Streichert, P. Jensen, J. Kietzerow, A. Mueller & S. Iwersen-Bergmann

  2. Institute of Legal Medicine, University Medical Center Hamburg—Eppendorf, Butenfeld 34, 22529, Hamburg, Germany

    M. Schrot & N. Wilke

  3. Department of Medical Biometry and Epidemiology, University Medical Center Hamburg—Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    E. Vettorazzi

Authors
  1. Hilke Andresen-Streichert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Kietzerow
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Schrot
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. Wilke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Vettorazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Iwersen-Bergmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hilke Andresen-Streichert.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andresen-Streichert, H., Jensen, P., Kietzerow, J. et al. Endogenous gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs. Int J Legal Med 129, 57–68 (2015). https://doi.org/10.1007/s00414-014-1051-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-014-1051-8

Keywords

Search

Navigation