Biomarkers of Gamma-Hydroxybutyric Acid (GHB) Exposure: A Comprehensive Review of Analytical and Forensic Advances

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid with both endogenous and exogenous origins, complicating its detection in clinical and forensic toxicology. Due to its rapid metabolism and short detection window in conventional biological matrices, identifying reliable biomarkers of GHB exposure is crucial. This literature review aims to assess current knowledge on potential GHB biomarkers that may extend the detection window or improve specificity. A systematic search of scientific databases was conducted to identify studies investigating GHB metabolites, conjugates, and related biochemical markers using advanced analytical techniques such as LC-MS/MS and GC-MS. The review highlights promising candidates, including glycolic acid, carnitin-GHB, and glycin-GHB, as well as 3,4-dihydroxybutyric acid, which show potential for distinguishing exogenous intake. However, significant interindividual variability and limited validation studies hinder their widespread implementation. Despite promising findings, further research is needed to confirm the specificity, stability, and reproducibility of these biomarkers. This review underscores the importance of developing standardized protocols to enhance GHB exposure detection in both clinical and forensic settings.