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Identification of new urinary gamma‐hydroxybutyric acid (GHB) markers applying untargeted metabolomics analysis following placebo‐controlled administration to humans


Steuer, Andrea E; Raeber, Justine; Steuer, Christian; Boxler, Martina I; Dornbierer, Dario A; Bosch, Oliver G; Quednow, Boris B; Seifritz, Erich; Kraemer, Thomas (2019). Identification of new urinary gamma‐hydroxybutyric acid (GHB) markers applying untargeted metabolomics analysis following placebo‐controlled administration to humans. Drug Testing and Analysis, 11(6):813-823.

Abstract

Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid that occurs naturally in the mammalian brain and that is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock-out drug in cases of drug facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 h in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use. In the framework of a randomized, placebo-controlled, crossover study in 20 healthy male volunteers, urine samples obtained 4.5 hours post-administration were submitted to untargeted mass spectrometry (MS, QTOF) analysis to identify possible new markers of GHB intake. MS data from four different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization) were filtered for significantly changed features applying uni- and multivariate statistics. From the resulting 42 compounds of interest, eight were finally identified including conjugates of GHB with carnitine, glutamate, and glycine as well as the endogenous compounds glycolate and succinylcarnitine. While GHB conjugates were only detectable in the GHB, but not in the placebo group, glycolate and succinylcarnitine were present in both groups albeit significantly increased through GHB intake. Untargeted metabolomics proved as a suitable tool for the non-hypothesis driven identification of new GHB markers. However, more studies on actual concentrations, detection windows, and stability will be necessary to assess the suitability of these markers for routine application.

Abstract

Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid that occurs naturally in the mammalian brain and that is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock-out drug in cases of drug facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 h in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use. In the framework of a randomized, placebo-controlled, crossover study in 20 healthy male volunteers, urine samples obtained 4.5 hours post-administration were submitted to untargeted mass spectrometry (MS, QTOF) analysis to identify possible new markers of GHB intake. MS data from four different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization) were filtered for significantly changed features applying uni- and multivariate statistics. From the resulting 42 compounds of interest, eight were finally identified including conjugates of GHB with carnitine, glutamate, and glycine as well as the endogenous compounds glycolate and succinylcarnitine. While GHB conjugates were only detectable in the GHB, but not in the placebo group, glycolate and succinylcarnitine were present in both groups albeit significantly increased through GHB intake. Untargeted metabolomics proved as a suitable tool for the non-hypothesis driven identification of new GHB markers. However, more studies on actual concentrations, detection windows, and stability will be necessary to assess the suitability of these markers for routine application.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
04 Faculty of Medicine > Neuroscience Center Zurich
04 Faculty of Medicine > Institute of Legal Medicine
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Analytical Chemistry, Spectroscopy, Pharmaceutical Science, Environmental Chemistry
Language:English
Date:June 2019
Deposited On:04 Jan 2019 15:47
Last Modified:07 Jun 2019 01:02
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1942-7603
Additional Information:This is the peer reviewed version of the following article: Drug Test Anal. 2018 Dec 12. doi: 10.1002/dta.2558, which has been published in final form at https://doi.org/10.1002/dta.2558. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. (http://www.wileyauthors.com/self-archiving)
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/dta.2558
PubMed ID:30548573

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