Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes

Figures & data

Figure 1. Acid catalysed interconversion of GHB to the cyclic ester GBL.

Table 1. Pharmacokinetic parameters of GHB in plasma from a double-blind randomized cross-over study involving eight male volunteers, who received sodium oxybate in the doses indicated. The results are (mean ± SD) from the study by Abanades et al. [43].

Pharmacokinetic parameter	Dose 40 mg/kg	Dose 50 mg/kg	Dose 60 mg/kg	Dose 72 mg/kg
Cmax (mg/L)	79.1 ± 26.4	83.1 ± 28.8	113.5 ± 20.1	130.1 ± 10.7
tmax (h)	0.7 ± 0.20	0.6 ± 0.10	0.6 ± 0.14	0.9 ± 0.20
AUC0–6 h (mg/L × h)	106.5 ± 6.7	143.7 ± 36.4	183.9 ± 47.0	301.1 ± 11.4
kel (h^−1)	0.98 ± 0.21	1.01 ± 0.18	1.06 ± 0.18	1.23 ± 0.11
Half-life (h)	0.73 ± 0.17	0.71 ± 0.15	0.67 ± 0.12	0.57 ± 0.05
Urinary excretion (0–6 h) (mg)	431 ± 202	706 ± 434	545 ± 107	919 ± 117
Urinary excretion (0–6 h) % of dose	1.6	1.98	1.50	1.90

Figure 2. Pharmacokinetic profiles of GHB in plasma from a controlled dosing study with 18 men and 18 women. The subjects received an oral dose of 4.5 g GHB as sodium oxybate [45]. The left plot shows concentration-time data plotted on a linear scale (zero-order elimination rate 18 mg/L/h) and the right plot is a semi-logarithmic scale (elimination half-life 39 min). The graph was re-drawn from reference [44].

Table 2. Comparison of endogenous concentrations of GHB in antemortem (AM) and postmortem (PM) biological specimens and suggested practical cut-off concentrations to use when analytical results are interpreted.

Antemortem or postmortem specimens	Endogenous concentration, mg/L	Recommended cut-off concentration, mg/L^a
Blood (AM)	<1.0	5
Blood (PM)^b	1–30^b	30–50^b
Urine (AM)	1–10	15
Urine (PM)	1–30	30
Vitreous humor (PM)	0.5–39	30
Breast Milk (AM)	0.13–1.03	5
Hair strands (AM)^c	0–12 ng/mg	Analysis of GHB in segments of hair along the shaft
Hair strands (PM)^c	0–12 ng/mg	No cut-off established (see text in manuscript)
Saliva (AM)	0.15–3.33	5
Cerebrospinal fluid (AM)	<1	5
Cerebrospinal fluid (PM)	0.5–24	10

^a No general consensus has been reached about the best analytical cut-off concentration that verifies exogenous intake of GHB. The values given in the table are based on a review of the literature and our own experiences in dealing with forensic cases.

^b The higher cut-off of 50 mg/L should be considered if heart blood was the specimen analysed and/or if there was a long postmortem interval and the body had undergone decomposition. A lower cut-off of 30 mg/L is suitable for short postmortem intervals and femoral venous blood.

^c GHB should be determined in ∼1 cm segments of hair along the shaft and results compared and contrasted.

Table 3. Summary statistics of age, gender and GHB concentrations in venous blood from people arrested in Sweden for driving under the influence of drugs [27].

Gender	Number of cases (%)	Mean age ± SD (range), y	Mean (median) conc., mg/L	Range of conc., mg/L
Males	736 (94%)^a	26.7 ± 5.8 (15–62)	90 (81)	8–600
Females	45 (6%)	33.2 ± 9.0 (19–55)^b	99 (100)^c	9–300
Both	781 (100)	27.1 ± 6.2 (15–62)	90 (82)	8–600

^a Much higher prevalence of male traffic offenders with GHB in blood (p < 0.001).

^b No significant difference in mean age of male and female traffic offenders (p > 0.05).

^c The median concentration of GHB in blood was not significantly different between males and females (p > 0.05).

Table 4. Summary statistics comparing postmortem concentrations of GHB in femoral blood when death was attributed to intoxication or other causes, such as trauma. Note that GHB was not necessarily the only drug present in these drug-related deaths [21].

Cause of death	Number of cases	Mean age ± SD (range), y	Mean (median) conc., mg/L	Range of conc., mg/L
Drug intoxication	51	29.2 ± 2.7 (15–52)	640 (280)	30–9200
Other causes	20	28.8 ± 9.0 (16–58)^a	93 (72)^b	30–210

^a No significant gender difference in mean age of victims (p > 0.05).

^b The median concentration of GHB in blood was significantly lower in other causes of death compared with intoxications (p < 0.001).

Table 5. Comparison of GHB concentrations in femoral blood and bladder urine in deaths attributed by medical examiners to drug intoxication or other causes of death, such as trauma [69].

Cause of death	Number of cases	Mean age ± SD (range), y	Mean (median) blood conc., mg/L	Mean (median) urine conc., mg/L
Drug intoxication	37	29.2 ± 9.2 (15–52)	637 (260)	2818 (1900)
Other causes	6	34.1 ± 12.3 (26–55)^a	73 (52)^b	316 (210)^c

^a No significant gender difference in mean age of victims (p > 0.05).

^b The median concentrations of GHB in blood and urine were significantly lower in other causes of death compared with drug intoxication (p < 0.001).

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