Skip to main content
SpringerLink
Log in

Forensic toxicology findings in deaths involving gamma-hydroxybutyrate

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

Abstract

Concentrations of the illicit drug gamma-hydroxybutyrate (GHB) were determined in femoral venous blood and urine obtained at autopsy in a series of GHB-related deaths (N = 49). The analysis of GHB was done by gas chromatography after conversion to gamma-butyrolactone and quantitation of the latter with a flame ionization detector. The cutoff concentration of GHB in femoral blood or urine for reporting positive results was 30 mg/L. The deceased were mainly young men (86%) aged 26.5 ± 7.2 years (mean ± SD), and the women (14%) were about 5 years younger at 21.4 ± 5.0 years. The mean, median, and highest concentrations of GHB in femoral blood (N = 37) were 294, 190, and 2,200 mg/L, respectively. The mean urine-to-blood ratio of GHB was 8.8, and the median was 5.2 (N = 28). In 12 cases, the concentrations of GHB in blood were negative (<30 mg/L) when the urine contained 350 mg/L on average (range 31–1,100 mg/L). Considerable poly-drug use was evident in these GHB-related deaths: ethanol (18 cases), amphetamine (12 cases), and various prescription medications (benzodizepines, opiates, and antidepressants) in other cases. Interpreting the concentrations of GHB in postmortem blood is complicated because of concomitant use of other psychoactive substances, variable degree of tolerance to centrally acting drugs, and the lack of reliable information about survival time after use of the drug.

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. Carai MA, Colombo G, Brunetti G et al (2001) Role of GABA(B) receptors in the sedative/hypnotic effect of gamma-hydroxybutyric acid. Eur J Pharmacol 428:315–321

    Article  CAS  PubMed  Google Scholar 

  2. Crunelli V, Emri Z, Leresche N (2006) Unravelling the brain targets of gamma-hydroxybutyric acid. Curr Opin Pharmacol 6:44–52

    Article  CAS  PubMed  Google Scholar 

  3. Drasbek KR, Christensen J, Jensen K (2006) Gamma-hydroxybutyrate—a drug of abuse. Acta Neurol Scand 114:145–156

    Article  CAS  PubMed  Google Scholar 

  4. Borgen LA, Cook HN, Hornfeldt CS et al (2002) Sodium oxybate (GHB) for treatment of cataplexy. Pharmacotherapy 22:798–799

    Article  PubMed  Google Scholar 

  5. Gallimberti L, Canton G, Gentile N et al (1989) Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Lancet 2:787–789

    Article  CAS  PubMed  Google Scholar 

  6. Johnson BA, Swift RM, Addolorato G et al (2005) Safety and efficacy of GABAergic medications for treating alcoholism. Alcohol Clin Exp Res 29:248–254

    Article  CAS  PubMed  Google Scholar 

  7. Persson SA, Eriksson A, Hallgren N et al (2001) GHB-dangerous, addictive and uncontrollable “party drug”. Lakartidningen 98:4026–4031 (4033–4025)

    CAS  PubMed  Google Scholar 

  8. Palmer RB (2004) Gamma-butyrolactone and 1,4-butanediol: abused analogues of gamma-hydroxybutyrate. Toxicol Rev 23:21–31

    Article  CAS  PubMed  Google Scholar 

  9. Zvosec DL, Smith SW, McCutcheon JR et al (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 

  10. Girard AL, Senn CY (2008) The role of the new “date rape drugs” in attributions about date rape. J Interpers Violence 23:3–20

    Article  PubMed  Google Scholar 

  11. Scott-Ham M, Burton FC (2005) Toxicological findings in cases of alleged drug-facilitated sexual assault in the United Kingdom over a 3-year period. J Clin Forensic Med 12:175–186

    Article  PubMed  Google Scholar 

  12. Abanades S, Farre M, Segura M et al (2006) Gamma-hydroxybutyrate (GHB) in humans: pharmacodynamics and pharmacokinetics. Ann N Y Acad Sci 1074:559–576

    Article  CAS  PubMed  Google Scholar 

  13. Borgen LA, Okerholm RA, Lai A et al (2004) The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients. J Clin Pharmacol 44:253–257

    Article  CAS  PubMed  Google Scholar 

  14. Borgen LA, Okerholm R, Morrison D et al (2003) The influence of gender and food on the pharmacokinetics of sodium oxybate oral solution in healthy subjects. J Clin Pharmacol 43:59–65

    Article  CAS  PubMed  Google Scholar 

  15. Timby N, Eriksson A, Bostrom K (2000) Gamma-hydroxybutyrate associated deaths. Am J Med 108:518–519

    Article  CAS  PubMed  Google Scholar 

  16. Knudsen K, Greter J, Verdicchio M (2008) High mortality rates among GHB abusers in western Sweden. Clin Toxicol (Phila) 46:187–192

    CAS  Google Scholar 

  17. Jones AW, Holmgren A, Kugelberg FC (2007) Gamma-hydroxybutyrate concentrations in the blood of impaired drivers, users of illicit drugs, and medical examiner cases. J Anal Toxicol 31:566–572

    CAS  PubMed  Google Scholar 

  18. Druid H, Holmgren P, Lowenhielm P (1996) Computer-assisted systems for forensic pathology and forensic toxicology. J Forensic Sci 41:830–836

    CAS  PubMed  Google Scholar 

  19. Schuberth J, Schuberth J (1989) Gas chromatographic-mass spectrometric determination of morphine, codeine and 6-monoacetylmorphine in blood extracted by solid phase. J Chromatogr 490:444–449

    Article  CAS  PubMed  Google Scholar 

  20. Kronstrand R, Jones AW (2000) Drugs of abuse, analysis. In: Siegel J, Saukko PJ, Knupeer GC (eds) Encyclopedia of forensic sciences. Academic, London, pp 598–610

    Google Scholar 

  21. Druid H, Holmgren P (1997) A compilation of fatal and control concentrations of drugs in postmortem femoral blood. J Forensic Sci 42:79–87

    PubMed  Google Scholar 

  22. Jones AW, Schuberth J (1989) Computer-aided headspace gas chromatography applied to blood-alcohol analysis: importance of online process control. J Forensic Sci 34:1116–1127

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  24. 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 

  25. Kintz P, Villain M, Cirimele V et al (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 

  26. Repetto MR, Repetto M (1997) Habitual, toxic, and lethal concentrations of 103 drugs of abuse in humans. J Toxicol Clin Toxicol 35:1–9

    Article  CAS  PubMed  Google Scholar 

  27. Schulz M, Schmoldt A (2003) Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie 58:447–474

    CAS  PubMed  Google Scholar 

  28. Stead AH, Moffat AC (1983) A collection of therapeutic, toxic and fatal blood drug concentrations in man. Hum Toxicol 2:437–464

    Article  CAS  PubMed  Google Scholar 

  29. Winek CL, Wahba WW, Winek CL Jr et al (2001) Drug and chemical blood-level data 2001. Forensic Sci Int 122:107–123

    Article  CAS  PubMed  Google Scholar 

  30. Ferner RE (2008) Post-mortem clinical pharmacology. Br J Clin Pharmacol 66:430–443

    Article  CAS  PubMed  Google Scholar 

  31. Iffland R, West A, Bilzer N et al (1999) Zur Zuverlässigkeit der Blutalkohol-bestimmung. Das Verteilungsverhältnis des Wassers zwischen Serum und Vollblut. Rechtsmedizin 9:123–130

    Article  Google Scholar 

  32. Drummer OH, Gerostamoulos J (2002) Postmortem drug analysis: analytical and toxicological aspects. Ther Drug Monit 24:199–209

    Article  CAS  PubMed  Google Scholar 

  33. Pounder DJ, Jones GR (1990) Post-mortem drug redistribution—a toxicological nightmare. Forensic Sci Int 45:253–263

    Article  CAS  PubMed  Google Scholar 

  34. Stephens BG, Coleman DE, Baselt RC (1999) In vitro stability of endogenous gamma-hydroxybutyrate in postmortem blood. J Forensic Sci 44:231

    CAS  PubMed  Google Scholar 

  35. Skopp G (2004) Preanalytic aspects in postmortem toxicology. Forensic Sci Int 142:75–100

    Article  CAS  PubMed  Google Scholar 

  36. Linnet K, Johansen SS, Buchard A et al (2008) Dominance of pre-analytical over analytical variation for measurement of methadone and its main metabolite in postmortem femoral blood. Forensic Sci Int 179:78–82

    Article  CAS  PubMed  Google Scholar 

  37. Prouty RW, Anderson WH (1990) The forensic science implications of site and temporal influences on postmortem blood-drug concentrations. J Forensic Sci 35:243–270

    CAS  PubMed  Google Scholar 

  38. Snead OC 3rd, Gibson KM (2005) Gamma-hydroxybutyric acid. N Engl J Med 352:2721–2732

    Article  CAS  PubMed  Google Scholar 

  39. Sporer KA, Chin RL, Dyer JE et al (2003) Gamma-hydroxybutyrate serum levels and clinical syndrome after severe overdose. Ann Emerg Med 42:3–8

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Caldicott DG, Chow FY, Burns BJ et al (2004) Fatalities associated with the use of gamma-hydroxybutyrate and its analogues in Australasia. Med J Aust 181:310–313

    PubMed  Google Scholar 

  42. Jones C (2001) Suspicious death related to gamma-hydroxybutyrate (GHB) toxicity. J Clin Forensic Med 8:74–76

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  44. 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

    CAS  PubMed  Google Scholar 

  45. Kintz P, Villain M, Pelissier AL et al (2005) Unusually high concentrations in a fatal GHB case. J Anal Toxicol 29:582–585

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

There was no external funding for this project, and none of the authors consider that they have a conflict of interest.

Author information

Authors and Affiliations

  1. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, 587 58, Linköping, Sweden

    Fredrik C. Kugelberg, Anita Holmgren, Arne Eklund & Alan Wayne Jones

Authors
  1. Fredrik C. Kugelberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anita Holmgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arne Eklund
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alan Wayne Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alan Wayne Jones.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM Table 2

(DOC 96 KB)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kugelberg, F.C., Holmgren, A., Eklund, A. et al. Forensic toxicology findings in deaths involving gamma-hydroxybutyrate. Int J Legal Med 124, 1–6 (2010). https://doi.org/10.1007/s00414-008-0299-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-008-0299-2

Keywords

Search

Navigation