Methyl-4-Hydroxybutyrate and Ethyl-4-Hydroxybutyrate as Potential Markers for Simultaneous Consumption of GHB/GBL and Alcohol: Preliminary Investigations

Theresa Küting, Niklas Beier, Michael Krämer, Burkhard Madea
Journal of Analytical Toxicology 2020 December 12, 44 (8): 818-828
γ-Hydroxybutyric acid (GHB) and its corresponding lactone γ-butyrolactone (GBL) are misused as knock out (k.o.) drugs. The short detection window and the major inter- and intra-individual variations of endogenous GHB concentrations in commonly used matrices such as blood and urine complicate the analytical proof of an exogenous GHB/GBL administration. We searched for an alternative way to prove an exogenous GHB/GBL administration via detection of methyl- and ethyl-4-hydroxybutyrate, which could arise in alcoholic solutions after spiking with GHB/GBL. A liquid chromatographic-triple quadrupole mass spectrometric method was developed and validated to quantitatively determine methyl- and ethyl-4-hydroxybutyrate in alcoholic beverages (limit of detection [LoD]: 5.8 and 3.4 ng/mL, respectively). A sample collective of alcoholic beverages (n = 47) revealed natural occurring amounts of ethyl-4-hydroxybutyrate (<LoD-approx. 3980 ng/mL) with higher concentrations particularly found in wine samples. Nearly no ethyl-4-hydroxybutyrate was observable in spirits/liqueurs and no methyl-4-hydroxybutyrate was detectable at all. A moderate correlation was shown between the ethyl-4-hydroxybutyrate concentration and the pH-value in wine samples (pH 2.9-3.7, n = 29) as well as between the ethyl-4-hydroxybutyrate concentration and the GHB concentration in all measured beverages (GHB:  <  limit of quantification [LoQ]-11.4 µg/mL, n = 47). A dependency on alcohol content could not be observed. A voluntary intake (n = 1) of 750-mL wine naturally containing high amounts of ethyl-4-hydroxybutyrate (approx. 2010 ng/mL) revealed no observable GHB-ester concentrations in blood and urine. Furthermore, an experiment simulating a beverage that could potentially be used in a drug-facilitated crime (DFC) case showed ethyl-4-hydroxybutyrate concentrations exceeding the concentrations naturally observed in beverage samples. However, in order to evaluate whether ethyl-4-hydroxybutyrate could be useful as marker for the co-consumption of GHB/GBL and alcohol and to prolong the detection window of unintended GHB/GBL intake, further experiments have to be performed.

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