Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes

Abstract

Introduction: c-Hydroxybutyric acid is an endogenous substance, a therapeutic agent, and a recreational drug of abuse. This psychoactive substance acts as a depressant of the central nervous system and is commonly encountered in clinical and forensic practice, including impaired drivers, poisoned patients, and drug-related intoxication deaths. Objective: The aim of this review is to assist clinical and forensic practitioners with the interpretation of c-hydroxybutyric acid concentrations in blood, urine, and alternative biological specimens from living and deceased persons. Methods: The information sources used to prepare this review were PubMed, Scopus, and Web-of-Science. These databases were searched using keywords c-hydroxybutyrate (GHB), blood, urine, alternative specimens, non-conventional biological matrices, saliva, oral fluid, sweat, hair, vitreous humor (VH), brain, cerebrospinal fluid (CSF), dried blood spots (DBS), breast milk, and various combinations thereof. The resulting 4228 references were screened to exclude duplicates, which left 1980 articles for further consideration. These publications were carefully evaluated by taking into account the main aims of the review and 143 scientific papers were considered relevant. Analytical methods: The analytical methods used to determine c-hydroxybutyric acid in blood and other biological specimens make use of gas-or liquid-chromatography coupled to mass spectrometry. These hyphenated techniques are accurate, precise, and specific for their intended purposes and the lower limit of quantitation in blood and other specimens is 0.5 mg/L or less. Human pharmacokinetics: GHB is rapidly absorbed from the gut and distributes into the total body water compartment. Only a small fraction of the dose (1-2%) is excreted unchanged in the urine. The plasma elimination half-life of c-hydroxybutyric acid is short, being only about 0.5-0.9 h, which requires timely sampling of blood and other biological specimens for clinical and forensic analysis. Endogenous concentrations of GHB in blood: GHB is both an endogenous metabolite and a drug of abuse, which complicates interpretation of the laboratory results of analysis. Moreover, the concentrations of GHB in blood and other specimens tend to increase after sampling, especially in autopsy cases. This requires the use of practical "cut-off" concentrations to avoid reporting false positive results. These cutoffs are different for different biological specimen types. Concentrations of GHB in clinical and forensic practice: As a recreational drug GHB is predominantly used by young males (94%) with a mean age of 27.1 years. The mean (median) and range of concentrations in blood from apprehended drivers was 90 mg/L (82 mg/L) and 8-600 mg/L, respectively. The concentration distributions in blood taken from living and deceased persons overlapped, although the mean (median) and range of concentrations were higher in intoxication deaths; 640 mg/ L (280 mg/L) and 30-9200 mg/L, respectively. Analysis of GHB in alternative specimens: All bi...

A fatal chemsex case involving γ‐butyrolactone and 4‐methylethcathinone

“…Concurrently, in deaths attributed to GHB intoxications, the mean and median values of GHB in femoral blood have been estimated at 637 and 260 μg/mL, respectively, while those in urine were 2800 and 1900 μg/mL …”

Prospective Investigation of the Performance of 2 Gamma-Hydroxybutyric Acid Tests: DrugCheck GHB Single Test and Viva-E GHB Immunoassay

“…However, the 50 mcg/mL cutoff is too high to draw conclusions on patient use of GHB because urine levels .10 mcg/mL are already associated with GHB intake. 10,[20][21][22][23] Secondary outcomes included the difference in ethanol levels between the false-positive and true-negative groups and possible interfering substances in the false-positive group.…”

“…By contrast, the Viva-E GHB immunoassay registered poor performance at a cutoff value of 10 mcg/mL and is therefore unable to detect exogenous GHB administration in cases of low urinary concentrations. 10,[20][21][22][23] Compared with the gas chromatography method used as the gold standard in this study, the main advantage of the investigated methods is the ability to obtain quicker test results. An on-site test for detecting urine GHB within minutes can be of great diagnostic value in addition to point-of-care tests for other drugs of abuse.…”

“…In the literature, urine clinical sample cutoff values of 10 and 15 mcg/mL have been described because endogenous concentrations in the urine vary between 1 and 10 mcg/mL. 10,[20][21][22][23] In this study, the aim was to prospectively investigate the performance of the new DrugCheck GHB Single Test and the Viva-E GHB immunoassay in urine sample analysis in ED patients. The DrugCheck GHB Single Test can be used by ED staff at point-of-care for generating results within 10 minutes, whereas the Viva-E GHB immunoassay, generally used in hospital laboratory settings, is an attractive alternative that can be used to generate results within 15 minutes.…”

Alcohol, its analysis in blood and breath for forensic purposes, impairment effects, and acute toxicity

“…Many of the signs and symptoms of acute alcohol intoxication are not unique to ethanol, because similar behavioral effects ensue after intake of other depressant drugs, such as benzodiazepines, barbiturates, and/or GHB (Busardo & Jones, ). The clinical diagnosis of alcohol intoxication requires careful documentation of the typical signs and symptoms of impairment and also verified by analysis of ethanol in a sample of blood or breath (Vonghia, Leggio, Ferrulli, Bertini et al, ).…”