Endogenous Levels, Detection Time, and Symptoms of Gamma-Hydroxybutyric Acid: Results From a Placebo-Controlled...

Gamma-hydroxybutyric acid (GHB), a potential agent in drug-facilitated sexual assault, is difficult to detect due to rapid elimination, endogenous presence, and possible postsampling formation. We conducted a randomised, placebo-controlled trial in 30 healthy volunteers, administering 50-mg/kg sodium oxybate or placebo, to investigate symptoms, pharmacokinetics and endogenous concentrations. Blood was collected in fluoride-oxalate (FX) tubes, and urine and oral fluid in additive-free tubes, at baseline, 1, 2, 3, 4, 6, 12, and 24 (urine only) hours post-administration. Samples were immediately cooled, stored at -70°C, and analysed using LC-MS/MS. Maximal endogenous GHB concentrations were 0.050 μg/mL in blood, 0.41 μg/mL in urine, and 0.93 μg/mL in oral fluid. GHB-treated participants reported vertigo and fatigue, with no significant memory impairment. Median peak GHB concentrations post-administration were 50, 440, and 29 μg/mL in blood, urine, and oral fluid, respectively. Oral fluid appeared unsuitable for GHB detection. As endogenous concentrations in blood did not exceed 0.050 μg/mL, a theoretical cut-off with a safety margin (0.25 μg/mL) would yield a negligible risk of false positives in samples collected in FX tubes and cooled immediately. Applying this cut-off extended the blood detection window ≥ 2 h in all GHB-treated participants, surpassing that in urine at a 6-μg/mL cut-off.