Towards Extending the Detection Window of Gamma-Hydroxybutyric Acid-An Untargeted Metabolomics Study in Serum and Urine Following Controlled Administration in Healthy Men

Overview

Journal Metabolites

Publisher MDPI

Date 2021 Apr 3

PMID 33809281

Citations 8

Authors

Andrea E Steuer

Justine Raeber

Fabio Simbuerger

Dario A Dornbierer

Oliver G Bosch

Boris B Quednow

Erich Seifritz

Thomas Kraemer

Affiliations

Soon will be listed here.

Abstract

In forensic toxicology, gamma-hydroxybutyrate (GHB) still represents one of the most challenging drugs of abuse in terms of analytical detection and interpretation. Given its rapid elimination, the detection window of GHB in common matrices is short (maximum 12 h in urine). Additionally, the differentiation from naturally occurring endogenous GHB, is challenging. Thus, novel biomarkers to extend the detection window of GHB are urgently needed. The present study aimed at searching new potential biomarkers of GHB use by means of mass spectrometry (MS) metabolomic profiling in serum (up to 16.5 h) and urine samples (up to 8 h after intake) collected during a placebo-controlled crossover study in healthy men. MS data acquired by different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization each) were filtered for significantly changed features applying univariate and mixed-effect model statistics. Complementary to a former study, conjugates of GHB with glycine, glutamate, taurine, carnitine and pentose (ribose) were identified in urine, with particularly GHB-pentose being promising for longer detection. None of the conjugates were detectable in serum. Therein, mainly energy metabolic substrates were identified, which may be useful for more detailed interpretation of underlying pathways but are too unspecific as biomarkers.

Citing Articles

A global perspective on the status of clinical metabolomics in laboratory medicine - a survey by the IFCC metabolomics working group.

Fux E, Lenski M, Bendt A, Otvos J, Ivanisevic J, De Bruyne S Clin Chem Lab Med. 2024; 62(10):1950-1961.

PMID: 38915248 DOI: 10.1515/cclm-2024-0550.

Urinary concentrations of GHB and its novel amino acid and carnitine conjugates following controlled GHB administration to humans.

Steuer A, Bavato F, Schnider L, Dornbierer D, Bosch O, Quednow B Sci Rep. 2023; 13(1):8983.

PMID: 37268859 PMC: 10238486. DOI: 10.1038/s41598-023-36213-1.

Small molecule metabolites: discovery of biomarkers and therapeutic targets.

Qiu S, Cai Y, Yao H, Lin C, Xie Y, Tang S Signal Transduct Target Ther. 2023; 8(1):132.

PMID: 36941259 PMC: 10026263. DOI: 10.1038/s41392-023-01399-3.

Extended Detection Window for Gamma-Hydroxybutyrate in the Urine of an Elderly Woman.

Berg J, Rajendiran R, Serkland T, Methlie C, Hallin E, Stokes C J Anal Toxicol. 2023; 47(4):e44-e47.

PMID: 36847150 PMC: 10324544. DOI: 10.1093/jat/bkad014.

Interaction between γ-Hydroxybutyric Acid and Ethanol: A Review from Toxicokinetic and Toxicodynamic Perspectives.

Jung S, Kim M, Kim S, Lee S Metabolites. 2023; 13(2).

PMID: 36837798 PMC: 9965651. DOI: 10.3390/metabo13020180.

References

Manier S, Meyer M . Current Situation of the Metabolomics Techniques Used for the Metabolism Studies of New Psychoactive Substances. Ther Drug Monit. 2019; 42(1):93-97. DOI: 10.1097/FTD.0000000000000694. View

Abanades S, Farre M, Segura M, Pichini S, Pastor A, Pacifici R . Disposition of gamma-hydroxybutyric acid in conventional and nonconventional biologic fluids after single drug administration: issues in methodology and drug monitoring. Ther Drug Monit. 2007; 29(1):64-70. DOI: 10.1097/FTD.0b013e3180307e5e. View

Kind T, Liu K, Lee D, DeFelice B, Meissen J, Fiehn O . LipidBlast in silico tandem mass spectrometry database for lipid identification. Nat Methods. 2013; 10(8):755-8. PMC: 3731409. DOI: 10.1038/nmeth.2551. View

Hanisch S, Stachel N, Skopp G . A potential new metabolite of gamma-hydroxybutyrate: sulfonated gamma-hydroxybutyric acid. Int J Legal Med. 2015; 130(2):411-4. DOI: 10.1007/s00414-015-1235-x. View

Ingels A, Wille S, Samyn N, Lambert W, Stove C . Screening and confirmation methods for GHB determination in biological fluids. Anal Bioanal Chem. 2014; 406(15):3553-77. DOI: 10.1007/s00216-013-7586-6. View

Maurer H . Analytical toxicology. Anal Bioanal Chem. 2007; 388(7):1311. DOI: 10.1007/s00216-007-1387-8. View

Wishart D, Tzur D, Knox C, Eisner R, Guo A, Young N . HMDB: the Human Metabolome Database. Nucleic Acids Res. 2007; 35(Database issue):D521-6. PMC: 1899095. DOI: 10.1093/nar/gkl923. View

Steuer A, Arnold K, Schneider T, Poetzsch M, Kraemer T . A new metabolomics-based strategy for identification of endogenous markers of urine adulteration attempts exemplified for potassium nitrite. Anal Bioanal Chem. 2017; 409(26):6235-6244. DOI: 10.1007/s00216-017-0567-4. View

Petersen I, Tortzen C, Kristensen J, Sejer Pedersen D, Breindahl T . Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide. J Anal Toxicol. 2013; 37(5):291-7. DOI: 10.1093/jat/bkt027. View

10.

Vanaveski T, Narvik J, Innos J, Philips M, Ottas A, Plaas M . Repeated Administration of D-Amphetamine Induces Distinct Alterations in Behavior and Metabolite Levels in 129Sv and Bl6 Mouse Strains. Front Neurosci. 2018; 12:399. PMC: 6005828. DOI: 10.3389/fnins.2018.00399. View

11.

Zheng T, Liu L, Shi J, Yu X, Xiao W, Sun R . The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse. Mol Biosyst. 2014; 10(7):1968-77. DOI: 10.1039/c4mb00158c. View

12.

Busardo F, Jones A . GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr Neuropharmacol. 2015; 13(1):47-70. PMC: 4462042. DOI: 10.2174/1570159X13666141210215423. View

13.

Guijas C, Montenegro-Burke J, Domingo-Almenara X, Palermo A, Warth B, Hermann G . METLIN: A Technology Platform for Identifying Knowns and Unknowns. Anal Chem. 2018; 90(5):3156-3164. PMC: 5933435. DOI: 10.1021/acs.analchem.7b04424. View

14.

Andresen H, Aydin B, Mueller A, Iwersen-Bergmann S . An overview of gamma-hydroxybutyric acid: pharmacodynamics, pharmacokinetics, toxic effects, addiction, analytical methods, and interpretation of results. Drug Test Anal. 2011; 3(9):560-8. DOI: 10.1002/dta.254. View

15.

Steuer A, Brockbals L, Kraemer T . Metabolomic Strategies in Biomarker Research-New Approach for Indirect Identification of Drug Consumption and Sample Manipulation in Clinical and Forensic Toxicology?. Front Chem. 2019; 7:319. PMC: 6523029. DOI: 10.3389/fchem.2019.00319. View

16.

Steuer A, Kaelin D, Boxler M, Eisenbeiss L, Holze F, Vizeli P . Comparative Untargeted Metabolomics Analysis of the Psychostimulants 3,4-Methylenedioxy-Methamphetamine (MDMA), Amphetamine, and the Novel Psychoactive Substance Mephedrone after Controlled Drug Administration to Humans. Metabolites. 2020; 10(8). PMC: 7465486. DOI: 10.3390/metabo10080306. View

17.

Sumner L, Amberg A, Barrett D, Beale M, Beger R, Daykin C . Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics. 2013; 3(3):211-221. PMC: 3772505. DOI: 10.1007/s11306-007-0082-2. View

18.

Perrine S, Michaels M, Ghoddoussi F, Hyde E, Tancer M, Galloway M . Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat. NMR Biomed. 2008; 22(4):419-25. PMC: 2882794. DOI: 10.1002/nbm.1352. View

19.

G Verstraete A . Detection times of drugs of abuse in blood, urine, and oral fluid. Ther Drug Monit. 2004; 26(2):200-5. DOI: 10.1097/00007691-200404000-00020. View

20.

Zheng T, Liu L, Aa J, Wang G, Cao B, Li M . Metabolic phenotype of rats exposed to heroin and potential markers of heroin abuse. Drug Alcohol Depend. 2012; 127(1-3):177-86. DOI: 10.1016/j.drugalcdep.2012.06.031. View