![handle is hein.journals/injlegame124 and id is 1 raw text is: Int J Legal Med (2010) 124:1-6
DOI 10.1007/s00414-008-0299-2
ORTIiNALI ARTICE
Forensic toxicology findings in deaths
involving gamma-hydroxybutyrate
Fredrik C. Kugelberg Anita Holmgren-
Arne Eklund Alan Wayne Jones
Received: 29 May 2008 /Accepted: 11 November 2008 /Published online: 2 December 2008
C Springer-Verlag 2008
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 con-
centrations 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 medica-
tions (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.
Electronic supplementary material The online version of this article
(doi:10.1007/s00414-008-0299-2) contains supplementary material,
which is available to authorized users.
F. C. Kugelberg A. Holmgren A. Eklund A. W. Jones (W)
Department of Forensic Genetics and Forensic Toxicology,
National Board of Forensic Medicine,
Artillerigatan 12,
587 58 Linkoping, Sweden
e-mail: wayne.jones@rmv.se
Keywords Autopsy Toxicology GHB Intoxication
Introduction
Gamma-hydroxybutyric acid (GHB) is an endogenous
metabolite formed during biosynthesis and degradation of
the major inhibitory neurotransmitter gamma-aminobutyric
acid [1, 2]. Medicolegal interest in GHB stems from its use
as an illicit recreational drug and powerful depressant of the
central nervous system. The mechanism of action of GHB
is similar to that of ethanol, barbiturates, and benzodiazepines
[3]. In some countries, GHB is also available on prescription
as sodium oxybate (Xyrem®), which is used to treat
cataplexy in patients suffering from narcolepsy [4]. Another
therapeutic application of GHB is in the field of addiction
medicine to relieve withdrawal symptoms and also help to
prevent relapse in recovering alcoholics [5, 6].
GHB was first classified as a scheduled substance in
Sweden in 2000 (class II) in an effort to curb its use as a
recreational drug [7]. However, abuse of GHB persists
because some people resort to using the pro-drugs, gamma-
butyrolactone (GBL) and 1,4-butanediol, both of which are
rapidly metabolized into GHB [8, 9]. Furthermore, GHB
has gained notoriety in the media as a so-called date-rape
drug, although evidence for its widespread use in chemical
submission is rather flimsy [10, 11]. The short elimination
half-life of GHB (30-40 min from plasma) means that body
fluids intended for toxicological analysis should be taken
without delay [12, 13]. The hepatic enzymes responsible for
metabolism of GHB become saturated after high doses, and
concentration time profiles in blood are best described by
nonlinear Michaelis-Menten kinetics rather than first-order
kinetics [14].
'_ Springer](ViewImageLocal?handle=hein.journals/injlegame124&div=1&collection=&method=preview&ext=.png&size=3)
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