TY - JOUR
T1 - Identification of a new metabolite of GHB
T2 - gamma-hydroxybutyric acid glucuronide
AU - Petersen, Ida Nymann
AU - Tortzen, Christian
AU - Kristensen, Jesper Langgaard
AU - Pedersen, Daniel Sejer
AU - Breindahl, Torben
PY - 2013/6
Y1 - 2013/6
N2 - 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 5 50). GHB-GLUC was found in concentrations ranging from 0.11 to 5.0 mg/mL (mean: 1.3+ 1.2 mg/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, GHBGLUC 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 mg/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.
AB - 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 5 50). GHB-GLUC was found in concentrations ranging from 0.11 to 5.0 mg/mL (mean: 1.3+ 1.2 mg/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, GHBGLUC 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 mg/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.
U2 - 10.1093/jat/bkt027
DO - 10.1093/jat/bkt027
M3 - Journal article
C2 - 23612681
SN - 0146-4760
VL - 37
SP - 291
EP - 297
JO - Journal of Analytical Toxicology
JF - Journal of Analytical Toxicology
IS - 5
ER -