Pharmacokinetic Properties of  -Hydroxybutyrate (GHB) in Whole Blood, Serum, and Urine

Abstract

Over the last 10-15 years, γ-hydroxybutyrate (GHB) and γ-butyrolactone have become increasingly popular "club drugs", but they have also gained attention as potential agents of drug-facilitated sexual assault (DFSA). Several studies have attempted to characterize GHB's pharmacokinetic properties in humans, and the aim of this paper is to build on this research with an emphasis on DFSA cases. A 25 mg/kg dose of GHB was given to 12 GHB-naïve volunteers (6 men and 6 women). Urine and blood samples (serum and whole blood) were collected and analyzed by gas chromatography-mass spectrometry following liquid-liquid extraction. The urinary T(max) was 1 h in 11 volunteers with a mean C(max) of 67.6 mg/L (32.6-161.3 mg/L). Urinary concentrations rapidly decreased to < 10 mg/L (interpretive limit) for 11 volunteers after just 4 h. Data derived from whole blood (mean C(max) = 48.0 mg/L, T(max) = 24.6 min) closely matched that from serum (mean C(max) = 59.4 mg/L, T(max) = 23.3 min), suggesting GHB is distributed into erythrocytes. All 12 volunteers had GHB concentrations of less than 5 mg/L in both whole blood and serum after 3 h. Results verify the rapid elimination of GHB and the limited retrospective power of a concentration-based approach to prove GHB administration in blood and urine and confirm that, in DFSA cases, samples should be collected as soon as possible.

Direct Monitoring of Exogenous γ-Hydroxybutyric Acid in Body Fluids by NMR Spectroscopy

“…1 H qNMR results were in accordance with those 300 reported by Brailsford et al, 15 in which aliquots of the same sample pool were analyzed. In that work, a wide pharmacokinetic study of GHB in different body fluids including urine was carried out.…”

“…0.1 mM) has been defined to distinguish external exposure from endogenous values. [15][16][17][18] With standard equipment for metabolomic studies (typically 500-600 MHz magnets with cryo-or conventional probes) concentrations up to the 0.1 mM could be detected and quantified.…”

Increases in Serum Growth Hormone Concentrations Associated with GHB Administration

“…Mean GHB concentrations for all twelve volunteers are plotted in Figure 3 and are reported in more detail elsewhere (18). GHB serum elimination profiles were similar in male (mean C max = 59.7 µg/mL) and female (mean C max = 59.2 µg/mL) volunteers.…”

“…Sample extraction, instrumental and data interpretation criteria are outlined in our previously published papers (14,18).…”

“…In the last 15 years GHB (and its related analogues such as gamma-butyrolactone (GBL)) has been linked to cases of drug-facilitated sexual assault (DFSA), more commonly termed "date-rape" (7)(8)(9)(10). In such cases toxicological proof of GHB administration is difficult due to its endogenous nature (0.2 -1 mg/L in urine), and rapid elimination from the body (half-life 20 -45 min), which results in a return to baseline concentrations in urine after only 8 hours post-administration (11)(12)(13)(14)(15)(16)(17)(18).…”