Initial evaluation of 4-palmitoyloxy butyrate in whole blood as potential biomarker after γ-hydroxybutyric acid intake

Jennifer Liut; Burkhard Madea; Dirk Meißner; Arne Lützen; Sirous Javidi; Cornelius Hess; Michael Krämer

doi:10.1093/jat/bkae095

Initial evaluation of 4-palmitoyloxy butyrate in whole blood as potential biomarker after γ-hydroxybutyric acid intake

J Anal Toxicol. 2024 Dec 10:bkae095. doi: 10.1093/jat/bkae095. Online ahead of print.

Authors

Jennifer Liut¹, Burkhard Madea¹, Dirk Meißner², Arne Lützen², Sirous Javidi³, Cornelius Hess⁴, Michael Krämer¹

Affiliations

¹ Institute of Forensic Medicine, Forensic Toxicology, University of Bonn, Stiftsplatz 12, 53111 Bonn, Germany.
² Kekulé-Institute for Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.
³ Hephata Hospital Schwalmstadt-Centre for sleep medicine, Hephata Hessian Diaconal Centre e.V., Schimmelpfengstr. 6, 34613 Schwalmstadt, Germany.
⁴ MVZ Dr. Stein and Colleagues, Division of Clinical and Forensic Toxicology, Tomphecke 45, 41169 Mönchengladbach, Germany.

PMID: 39658023
DOI: 10.1093/jat/bkae095

Abstract

The problem of finding a suitable biomarker to widen the detection window of γ-hydroxybutyric acid (GHB) intake remains a challenge in forensic toxicology. Based on previously published results, the present study deals with the evaluation of a fatty acid ester of GHB (4-palmitoyloxy butyrate (GHB-Pal)) in whole blood as a potential biomarker to extend the detection window of GHB use e.g. in drug-facilitated sexual assaults (DFSA). A liquid chromatography-mass spectrometry (LC-MS/MS) method for the quantification of GHB-Pal in whole blood was validated. Whole blood samples were collected from subjects involed in police roadside controls (n=113) and from narcolepsy patients (n=10) after the controlled administration of Xyrem® (sodium oxybate). Both sample collectives were previously tested for GHB using two different methods: ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS). In samples from routine police casework, GHB-Pal was detected in 67 out of 113 analysed GHB-positive samples with a mean concentration of 0.8 ng/mL ± 0.5 ng/mL (standard deviation). Among samples that were tested positive for both compounds, no linear correlation was observed between GHB and GHB-Pal concentrations (r=0.508). In contrast, GHB-Pal was not detected in any of the blood samples analysed from the patients. The absence of GHB and GHB-Pal in the patient cohort may be attributed to the time interval between dose intake and blood collection (approx. 3 and 6 h), during which GHB was eliminated from the body. Furthermore, GHB-Pal was only detectable at a GHB concentration of at least 16 µg/mL, which indicates that endogenous concentrations or low GHB doses may not be sufficient for GHB-Pal formation. Due to missing correlation between both compounds and the lack of GHB-Pal detection several hours after GHB administration, it can be assumed that GHB-Pal in blood is not a suitable biomarker to widen the detection window of GHB.

© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact [email protected].