Source inference of exogenous gamma-hydroxybutyric acid (GHB) administered to humans by means of carbon isotopic ratio analysis: novel perspectives regarding forensic investigation and intelligence issues

Abstract

γ-Hydroxybutyric acid (GHB) is an endogenous short-chain fatty acid popular as a recreational drug due to sedative and euphoric effects, but also often implicated in drug-facilitated sexual assaults owing to disinhibition and amnesic properties. Whilst discrimination between endogenous and exogenous GHB as required in intoxication cases may be achieved by the determination of the carbon isotope content, such information has not yet been exploited to answer source inference questions of forensic investigation and intelligence interests. However, potential isotopic fractionation effects occurring through the whole metabolism of GHB may be a major concern in this regard. Thus, urine specimens from six healthy male volunteers who ingested prescription GHB sodium salt, marketed as Xyrem(®), were analysed by means of gas chromatography/combustion/isotope ratio mass spectrometry to assess this particular topic. A very narrow range of δ(13)C values, spreading from -24.81‰ to -25.06‰, was observed, whilst mean δ(13)C value of Xyrem(®) corresponded to -24.99‰. Since urine samples and prescription drug could not be distinguished by means of statistical analysis, carbon isotopic effects and subsequent influence on δ(13)C values through GHB metabolism as a whole could be ruled out. Thus, a link between GHB as a raw matrix and found in a biological fluid may be established, bringing relevant information regarding source inference evaluation. Therefore, this study supports a diversified scope of exploitation for stable isotopes characterized in biological matrices from investigations on intoxication cases to drug intelligence programmes.

Complementary approach for accurate determination of carbon isotopic compositions in γ‐hydroxybutyric acid using gas chromatography/combustion‐isotope ratio mass spectrometry

“…For instance, after ingestion of GHB (25 mg/kg dose), concentrations in urine and blood samples obtained from some volunteers rapidly decreased to <10 ppm after 4 h . Actually, the GHB concentrations preserved in seized urine samples have often yielded low concentrations (less than 10 ppm) due to unavoidable delays of several hours prior to sample collection . Thus, the methodology first applied in this study could improve the determination of exogenous GHB present in varying concentrations (especially low concentrations).…”

“…On the other hand, the carbon isotopic compositions (δ 13 C values) of GHB have been employed to separate blood samples derived from endogenous GHB production and those from exogenous abuse, showing a significant isotopic difference (17.1 ± 1.7‰), because the isotope approach can be independent of sample quantity. The isotopic approach is known to effectively distinguish various carbon sources, which reflect dietary or non‐dietary origin, as well as GHB synthesis routes via naturally occurring chemical precursors such as γ‐butyrolactone and 1,4‐butanediol . Accordingly, the use of GHB δ 13 C values can be an alternative way to overcome the limitations of a quantitative approach …”

“…The isotopic approach is known to effectively distinguish various carbon sources, which reflect dietary or non‐dietary origin, as well as GHB synthesis routes via naturally occurring chemical precursors such as γ‐butyrolactone and 1,4‐butanediol . Accordingly, the use of GHB δ 13 C values can be an alternative way to overcome the limitations of a quantitative approach …”

“…The isotopic approach is known to effectively distinguish various carbon sources, which reflect dietary or non-dietary origin, as well as GHB synthesis routes via naturally occurring chemical precursors such as γ-butyrolactone and 1,4-butanediol. [12][13][14][15] Accordingly, the use of GHB δ 13 C values can be an alternative way to overcome the limitations of a quantitative approach. 12,13,15 With the isotopic approach, using gas chromatography/ combustion-isotope ratio mass spectrometry (GC/C-IRMS), methodological developments have improved the accuracy of isotopic measurements.…”

Increasing the linear dynamic range in LC–MS: is it valid to use a less abundant isotopologue?

“…This research has focussed mainly on comparing illicit drug seizures with regard to their source. A survey of the literature revealed a large number of measured isotope ratios for individual drug and drug precursor samples . The isotope ratio variation for carbon ( n = 883), nitrogen ( n = 709), and hydrogen ( n = 567) are shown in Figure .…”