Abstract
GHB is an endogenous short-chain organic acid presumably also widely applied as a rape and knock out drug in cases of drug-facilitated crimes or sexual assaults (DFSA). Due to the endogenous nature of GHB and its fast metabolism in vivo, the detection window of exogenous GHB is however narrow, making it challenging to prove use of GHB in DFSA cases. Alternative markers of GHB intake have recently appeared though none has hitherto been validated for forensic use. UHPLC-HRMS based screening of blood samples for drugs of abuse is routinely performed in several forensic laboratories which leaves an enormous amount of unexploited data. Recently we devised a novel metabolomics approach to use archived data from such routine screenings for elucidating both direct metabolites from exogenous compounds, but potentially also regulation of endogenous metabolism and metabolites. In this paper we used UHPLC-HRMS data acquired over a 6-year period from whole blood analysis of 51 drivers driving under the influence of GHB as well as a matched control group. The data were analyzed using a metabolomics approach applying a range of advanced analytical methods such as OPLS-DA, LASSO, random forest, and Pearson correlation to examine the data in depth and demonstrate the feasibility and potential power of the approach. This was done by initially detecting a range of potential biomarkers of GHB consumption, some that previously have been found in controlled GHB studies, as well as several new potential markers not hitherto known. Furthermore, we investigate the impact of GHB intake on human metabolism. In aggregate, we demonstrate the feasibility to extract meaningful information from archived data here exemplified using GHB cases. Hereby we hope to pave the way for more general use of the principle to elucidate human metabolites of e.g. new legal or illegal drugs as well as for applications in more global and large scale metabolomics studies in the future.
Highlights
Gamma-hydroxybutyrate (GHB) is an endogenous shortchain organic acid derived from γ-aminobutyric acid (GABA) in the brain and periphery (Struys et al, 2006)
retention time (RT) deviates with a maximum of 20 s before peak alignment, which indicates the variation between samples
The current findings further suggest that whole blood GHB-carnitine could be a potential marker for exogenous GHB intake
Summary
Gamma-hydroxybutyrate (GHB) is an endogenous shortchain organic acid derived from γ-aminobutyric acid (GABA) in the brain and periphery (Struys et al, 2006). GHB, or more recently its lactone prodrug γbutyrolactone (GBL), is consumed recreationally as a drug of abuse, and is known as a rape drug and knock out drug in cases of drug-facilitated crimes or sexual assaults (DFSA) in forensic toxicology the frequency apparently is low (Epperson and Ralston, 2016; Francesco et al, 2018). The low frequency of detection may be caused by the fast metabolism and thereby narrow detection window of typically up to 6 h in whole blood and 12 h in urine (Busardò and Jones, 2019). Many DFSA cases are likely reported late causing blood or urine samples to be drawn too late for detection of exogenous GHB intake (Kintz et al, 2001; Odujebe et al, 2007; Busardò and Jones, 2019). The detection of GHB, discrimination between endogenous and exogenous GHB, and subsequently proving the ingestion of exogenous origin is challenging and likely underreported (Brenneisen et al, 2004; Abanades et al, 2007)
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