title: Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide.
abstract: Gamma-hydroxybutyric acid (GHB) is an important analyte in clinical and forensic toxicology with a narrow detection window of 3-6 h. In the search of improved detection methods, the existence in vivo of a glucuronated GHB metabolite (GHB-GLUC) was hypothesized. Chemically pure standards of GHB-GLUC and a deuterated analogue for chromatography were synthesized. Liquid chromatography and tandem mass spectrometry were used for targeted analysis in anonymous clinical urine samples (n = 50). GHB-GLUC was found in concentrations ranging from 0.11 to 5.0 µg/mL (mean: 1.3 ± 1.2 µg/mL). Thus far, this is the first report of a GHB glucuronide detected in biological samples. Given that glucuronides generally have longer half-life values than their corresponding free drugs, GHB-GLUC should theoretically be a biomarker of GHB intoxication. It is also proposed that the hitherto unexplained reports of elevated GHB concentrations in some biological samples, which has caused the setting of a relatively high cutoff value (10 µg/mL), represent total GHB measurements (sum of free GHB and actively chemically hydrolyzed GHB-GLUC). To address these challenges, the present study must be followed by comprehensive pharmacokinetic and stability studies after the controlled administration of GHB.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ida Nymann
authors.initials: IN
authors.lastname: Petersen
authors.forename: Christian
authors.initials: C
authors.lastname: Tortzen
authors.forename: Jesper Langgaard
authors.initials: JL
authors.lastname: Kristensen
authors.forename: Daniel Sejer
authors.initials: DS
authors.lastname: Pedersen
authors.forename: Torben
authors.initials: T
authors.lastname: Breindahl
mesh_terms: D035041:Anonymous Testing; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003903:Deuterium / Q000737:chemistry; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D006207:Half-Life; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D015203:Reproducibility of Results; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D020719:Glucuronides; D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; D003903:Deuterium