Fatty acid esters as novel metabolites of γ-hydroxybutyric acid: A preliminary investigation.
GHB
detection window
fatty acid ester
metabolites
γ-hydroxybutyric acid
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
revised:
01
12
2021
received:
20
10
2021
accepted:
11
12
2021
pubmed:
5
1
2022
medline:
12
4
2022
entrez:
4
1
2022
Statut:
ppublish
Résumé
γ-Hydroxybutyric acid (GHB) is a substance frequently abused as a knockout agent. Because of possible amnesia experienced by victims of GHB exposure and the short detection time of GHB in biological samples, the proof of GHB uptake is often challenging for forensic toxicologists. For this reason, various approaches have been evaluated to prolong the detection of GHB intake. In the present study, a fatty acid ester of GHB (4-palmitoyloxy butyrate [GHB-Pal; 3-carboxypropyl hexadecanoate]) was synthesized with the intent of examining whether such esters could be detected as metabolites of GHB in blood samples. Using the structurally elucidated synthesis product (structural elucidation by means of high performance liquid chromatography quadrupole time of flight mass spectrometry [LC-QToF-MS]), an LC triple quadrupole mass spectrometric (LC-MS/MS) method was established for the detection of GHB-Pal. Blood (plasma) samples from four cases in which GHB was previously detected at relevant concentrations (56.1-96.5 μg/ml) were analyzed with respect to GHB-Pal. Signals for GHB-Pal, as well as possible signals for other fatty acid esters of GHB, were detectable in these specimens. (Negative) control samples (20 plasma samples and 20 red blood cell/blood clot samples; from cases in which an intake of GHB or its precursors was not assumed) were all negative for GHB-Pal. To evaluate a possible forensic benefit of GHB fatty acid esters (prolongation of the detection window of a GHB uptake), the analysis of additional plasma samples collected after GHB uptake (or controlled GHB administration) and quantification of GHB fatty acid esters are needed.
Substances chimiques
Esters
0
Hydroxybutyrates
0
4-hydroxybutyric acid
30IW36W5B2
Sodium Oxybate
7G33012534
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
690-700Informations de copyright
© 2022 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
Références
Busardo FP, Jones AW. 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.
Madea B, Musshoff F. Knock-out drugs: their prevalence, modes of action, and means of detection. Dtsch Arztebl Int. 2009;106(20):341-347.
Küting T, Krämer M, Bicker W, Madea B, Hess C. Case report: another death associated to γ-hydroxybutyric acid intoxication. Forensic Sci Int. 2019;299:34-40.
Andresen H, Aydin BE, 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):560-568.
Andresen H, Sprys N, Schmoldt A, Mueller A, Iwersen-Bergmann S. Gamma-hydroxybutyrate in urine and serum: additional data supporting current cut-off recommendations. Forensic Sci Int. 2010;200(1-3):93-99.
Elliott SP. Gamma hydroxybutyric acid (GHB) concentrations in humans and factors affecting endogenous production. Forensic Sci Int. 2003;133(1-2):9-16.
Kintz P, Cirimele V, Jamey C, Ludes B. Testing for GHB in hair by GC/MS/MS after a single exposure. Application to document sexual assault. J Forensic Sci. 2003;48(1):1-6.
Busardò FP, Pichini S, Zaami S, Pacifici R, Kintz P. Hair testing of GHB: an everlasting issue in forensic toxicology. Clin Chem Lab Med. 2018;56(2):198-208.
Martz W, Nebel A, Veit F. Variation of intraindividual levels of endogenous GHB in segmented hair samples. Forensic Sci Int. 2019;302:109913
Mehling L-M, Wang X, Johansen S-S, et al. Determination of GHB and GHB-β-O-glucuronide in hair of three narcoleptic patients-comparison between single and chronic GHB exposure. Forensic Sci Int. 2017;278:e8-e13.
Nebel A, Mayer G, Hess C, Heidbreder A, Martz W, Veit F. Levels of GHB in hair after regular application. Forensic Sci Int. 2021;325:110885
Mehling L-M, Piper T, Spottke A, et al. GHB-O-β-glucuronide in blood and urine is not a suitable tool for the extension of the detection window after GHB intake. Forensic Toxicol. 2017;35(2):263-274.
Piper T, Mehling L-M, Spottke A, et al. Potential of GHB phase-II-metabolites to complement current approaches in GHB post administration detection. Forensic Sci Int. 2017;279:157-164.
Larson SJ, Putnam EA, Schwanke CM, Pershouse MA. Potential surrogate markers for gamma-hydroxybutyrate administration may extend the detection window from 12 to 48 hours. J Anal Toxicol. 2007;31(1):15-22.
Mehling L-M, Spottke A, Heidbreder A, et al. Alterations in gene expression after gamma-hydroxybutyric acid intake-a pilot study. Int J Leg Med. 2017;131(5):1261-1270.
Steuer AE, Raeber J, Steuer C, et al. Identification of new urinary gamma-hydroxybutyric acid markers applying untargeted metabolomics analysis following placebo-controlled administration to humans. Drug Test Anal. 2019;11(6):813-823.
Hennessy SA, Moane SM, McDermott SD. The reactivity of gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) in alcoholic solutions. J Forensic Sci. 2004;49(6):1220-9.
Küting T, Beier N, Krämer M, Madea B. Methyl-4-hydroxybutyrate and ethyl-4-hydroxybutyrate as potential markers for simultaneous consumption of GHB/GBL and alcohol: preliminary investigations. J Anal Toxicol. 2020;44(8):818-828.
Jarsiah P, Roehrich J, Wyczynski M, Hess C. Phase I metabolites (organic acids) of gamma-hydroxybutyric acid-validated quantification using GC-MS and description of endogenous concentration ranges. Drug Test Anal. 2020;12(8):1135-1143.
Küting T, Schneider B, Heidbreder A, et al. Detection of GHB-related acids in blood plasma and urine: extending the detection window of an exogenous GHB intake? Drug Test Anal. 2021;13(9):1635-1649.
Auwärter V, Sporkert F, Hartwig S, Pragst F, Vater H, Diefenbacher A. Fatty acid ethyl esters in hair as markers of alcohol consumption. Segmental hair analysis of alcoholics, social drinkers, and teetotalers. Clin Chem. 2001;47(12):2114-2123.
Pragst F, Rothe M, Moench B, Hastedt M, Herre S, Simmert D. Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages. Forensic Sci Int. 2010;196(1-3):101-110.
Doyle KM, Bird DA, al-Salihi S, et al. Fatty acid ethyl esters are present in human serum after ethanol ingestion. J Lipid Res. 1994;35(3):428-437.
Doyle KM, Cluette-Brown JE, Dube DM, Bernhardt TG, Morse CR, Laposata M. Fatty acid ethyl esters in the blood as markers for ethanol intake. JAMA. 1996;276(14):1152-1156.
Dan L, Laposata M. Ethyl palmitate and ethyl oleate are the predominant fatty acid ethyl esters in the blood after ethanol ingestion and their synthesis is differentially influenced by the extracellular concentrations of their corresponding fatty acids. Alcohol Clin Exp Res. 1997;21(2):286-292.
Peters FT, Drummer OH, Musshoff F. Validation of new methods. Forensic Sci Int. 2007;165(2-3):216-224.
Peters FT, Hartung M, Herbold M, Schmitt G, Daldrup T, Musshoff F. Anhang B zur Richtlinie der GTFCh zur Qualitätssicherung bei forensisch-toxikologischen Untersuchungen: Anforderungen an die Validierung von Analysenmethoden. Toxichem Krimtech. 2009;76(3):185-208.
Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC−MS/MS. Anal Chem. 2003;75(13):3019-3030.
Ciolino LA, Mesmer MZ, Satzger RD, Machal AC, McCauley HA, Mohrhaus AS. The chemical interconversion of GHB and GBL: forensic issues and implications. J Forensic Sci. 2001;46(6):1315-1323.
Zhang T, Chen S, Syed I, et al. A LC-MS-based workflow for measurement of branched fatty acid esters of hydroxy fatty acids. Nat Protoc. 2016;11(4):747-763.
Paul LD, Musshoff F. Richtlinie der GTFCh zur Qualitätssicherung bei forensisch-toxikologischen Untersuchungen. Toxichem Krimtech. 2009;76(3):142-176.
Brogan WC III, Kemp PM, Bost RO, Glamann DB, Lange RA, Hillis LD. Collection and handling of clinical blood samples to assure the accurate measurement of cocaine concentration. J Anal Toxicol. 1992;16(3):152-154.
Soderberg BL, Sicinska ET, Blodget E, et al. Preanalytical variables affecting the quantification of fatty acid ethyl esters in plasma and serum samples. Clin Chem. 1999;45(12):2183-2190.