Skip to main content
SpringerLink
Log in

Comparison of endogenous GHB concentrations in blood and hair in death cases with emphasis on the post mortem interval

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

Abstract

Gamma-hydroxybutyric acid (GHB) is an endogenous compound which has a story of clinical use and illicit abuse since the 1960’s. The possibility to use a multi-sample approach for GHB evaluation, including whole blood and hair, to better characterize a forensic toxicology case and evaluate a possible causal association with the death is an exciting up-to-date issue. In addition, its post-mortem behaviour, namely regarding degradation and metabolism, has been increasingly investigated as a putative biomarker for post-mortem interval (PMI) estimation. Thus, in order to contribute to clarification of this specific aspect, whole blood and hair post-mortem GHB levels were evaluated in 32 real cases with previous information on death and autopsy data. The results obtained suggest that the PMI (until 5 days between death and sampling) influences GHB whole blood concentration, but not GHB levels in hair samples. No differences were encountered for the other parameters evaluated, including age, gender, cause of death and presence or absence of substances. This study brings new insights regarding the usefulness of GHB levels in forensic toxicology, which might be further strengthened with larger, but comparable, studies from other laboratories and institutions in the context of legal medicine.

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

Similar content being viewed by others

Abbreviations

BSTFA:

N,O-bis(trimethylsilyl)-trifluoroacetamide

F:

Female

GC-MS/MS:

Gas chromatography–tandem mass spectrometry

GHB:

Gamma-hydroxybutyric acid

GHB-D6:

Deuterated gamma-hydroxybutyric acid

LOD:

Limit of detection

LLOQ:

Lower limit of quantitation

M:

Male

min:

Minutes

m/z:

Mass-to-charge ratio

n:

Number of cases

PMI:

Post-mortem interval

SD:

Standard deviation

TMCS:

Trimethylchlorosilane

WB:

Whole blood

References

  1. 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. doi:10.1016/j.forsciint.2004.02.036

    Article  CAS  Google Scholar 

  2. 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

    Article  CAS  Google Scholar 

  3. Castro AL, Dias M, Reis F, Teixeira HM (2014) Gamma-hydroxybutyric acid endogenous production and postmortem behavior - the importance of different biological matrices, cut-off reference values, sample collection and storage conditions. J Forensic Leg Med 27:17–24. doi:10.1016/j.jflm.2014.07.008

    Article  Google Scholar 

  4. Goullé JP, Chèze M, Pépin G (2003) Determination of endogenous levels of GHB in human hair. Are there possibilities for the identification of GHB administration through hair analysis in cases of drug-facilitated sexual assault? J Anal Toxicol 27:574–580

    Article  Google Scholar 

  5. Paul R, Tsanaclis L, Kingston R, Berry A, Guwy A (2011) Simultaneous determination of GHB and EtG in hair using GCMS/MS. Drug Test Anal 3:201–205. doi:10.1002/dta.172

    Article  CAS  Google Scholar 

  6. Fjeld B, Burns ML, 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 222:47–51. doi:10.1016/j.forsciint.2012.04.033

    Article  Google Scholar 

  7. Elliott S, Lowe P, Symonds A (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. doi:10.1016/j.forsciint.2003.10.018

    Article  CAS  Google Scholar 

  8. Busardò F, Bertol E, Vaiano F, Baglio G, Montana A, Barbera N, Zaami S, Romano G (2014) Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in vitro formation in stored blood and urine samples. Forensic Sci Int 243:144–148

    Article  Google Scholar 

  9. Moriya F, Hashimoto Y (2004) Endogenous γ-hydroxybutyric acid levels in postmortem blood. Leg Med 6:47–51. doi:10.1016/j.legalmed.2003.09.004

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Richard D, Ling B, Authier N, Faict TW, Eschalier A, Coudoré F (2005) GC/MS profiling of γ-hydroxybutyrate and precursors in various animal tissues using automatic solid-phase extraction. preliminary investigations of its potential interest in postmortem interval determination. Anal Chem 77:1354–1360. doi:10.1021/ac048471h

    Article  CAS  Google Scholar 

  12. Maxwell JC (2005) Party drugs: properties, prevalence, patterns and problems. Subst Use Misuse 40:1203–1240

    Article  Google Scholar 

  13. 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  Google Scholar 

  14. Castro A, Tarelho S, Dias M, Reis F, Teixeira HM (in press) A fast and reliable method for GHB quantitation in whole blood by GC-MS/MS (TQD) for forensic purposes. J Pharm Biomed Anal (in press) doi:10.1016/j.jpba.2015.11.038.

  15. Kintz P, Cirimele V, Jamey C, Ludes B (2003) Testing for GHB in hair by GC/MS/MS after a single exposure. Application to document sexual assault. J Forensic Sci 48:1–6

    Article  Google Scholar 

  16. Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224. doi:10.1016/j.forsciint.2006.05.021

    Article  CAS  Google Scholar 

  17. Gu H, Liu G, Wang J, Aubry AF, Arnold ME (2014) Selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays and impacts of using incorrect weighting factors on curve stability, data quality, and assay performance. Anal Chem 86:8959–8966. doi:10.1021/ac5018265

  18. Couper FJ, Marinetti LJ (2002) γ-Hydroxybutyrate (GHB) – Effects on human performance and behavior. Forensic Sci Rev 14:101–121

    CAS  PubMed  Google Scholar 

  19. 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(1–3):93–99. doi:10.1016/j.forsciint.2010.03.035

    Article  CAS  Google Scholar 

  20. Korb AS, Cooper G (2014) Endogenous concentrations of GHB in postmortem blood from deaths unrelated to GHB use. J Anal Toxicol 38:582–588. doi:10.1093/jat/bku088

    Article  CAS  Google Scholar 

  21. Moriya F, Hashimoto Y (2005) Site-dependent production of γ-hydroxybutyric acid in the early postmortem period. Forensic Sci Int 148:139–142. doi:10.1016/j.forsciint.2004.05.002

    Article  CAS  Google Scholar 

  22. Andresen-Streichert H, Jensen P, Kietzerow J, Schrot M, Wilke N, Vettorazzi E, Mueller A, Iwersen-Bergmann S (2015) Endogenous gammahydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs. Int J Legal Med 129:57–68. doi:10.1007/s00414-014-1051-8

    Article  Google Scholar 

  23. Bertol E, Mari F, Vaiano F, Romano G, Zaami S, Baglìod G, Busardò FP (2014) Determination of GHB in human hair by HPLC-MS/MS: development and validation of a method and application to a study group and three possible single exposure cases. Drug Test Anal 7(5):376–384. doi:10.1002/dta.1679

    Article  Google Scholar 

  24. Petersen IN, Tortzen C, Kristensen JL, Pedersen DS, Breindahl T (2013) Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide. J Anal Toxicol 37(5):291–297. doi:10.1093/jat/bkt027

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Portuguese Foundation for Science and Technology (FCT) through UID/NEU/04539/2013 (CNC.IBILI).

Author information

Authors and Affiliations

  1. National Institute of Legal Medicine and Forensic Sciences, Porto, Portugal

    André L. Castro, Sónia Tarelho, Mário Dias & Helena M. Teixeira

  2. Faculty of Medicine, University of Porto, Porto, Portugal

    André L. Castro & Helena M. Teixeira

  3. Laboratory of Pharmacology & Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (CNC.IBILI Research Consortium), Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Flávio Reis

  4. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Helena M. Teixeira

Authors
  1. André L. Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sónia Tarelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mário Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Flávio Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helena M. Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to André L. Castro.

Additional information

Manuscript’s highlights

• Analysis of post-mortem whole blood and hair real case samples.

• Statistical evaluation of the results.

• Application to post-mortem interval estimation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Castro, A.L., Tarelho, S., Dias, M. et al. Comparison of endogenous GHB concentrations in blood and hair in death cases with emphasis on the post mortem interval. Int J Legal Med 130, 959–965 (2016). https://doi.org/10.1007/s00414-016-1321-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-016-1321-8

Keywords

Search

Navigation