title: Carbon isotopic ratio analysis by gas chromatography/combustion/isotope ratio mass spectrometry for the detection of gamma-hydroxybutyric acid (GHB) administration to humans.
abstract: Since GHB (gamma-hydroxybutyric acid) is naturally produced in the human body, clinical and forensic toxicologists must be able to discriminate between endogenous levels and a concentration resulting from exposure. To suggest an alternative to the use of interpretative concentration cut-offs, the detection of exogenous GHB in urine specimens was investigated by means of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). GHB was isolated from urinary matrix by successive purification on Oasis MCX and Bond Elute SAX solid-phase extraction (SPE) cartridges prior to high-performance liquid chromatography (HPLC) fractioning using an Atlantis dC18 column eluted with a mixture of formic acid and methanol. Subsequent intramolecular esterification of GHB leading to the formation of gamma-butyrolactone (GBL) was carried out to avoid introduction of additional carbon atoms for carbon isotopic ratio analysis. A precision of 0.3 per thousand was determined using this IRMS method for samples at GHB concentrations of 10 mg/L. The (13)C/(12)C ratios of GHB in samples of subjects exposed to the drug ranged from -32.1 to -42.1 per thousand, whereas the results obtained for samples containing GHB of endogenous origin at concentration levels less than 10 mg/L were in the range -23.5 to -27.0 per thousand. Therefore, these preliminary results show that a possible discrimination between endogenous and exogenous GHB can be made using carbon isotopic ratio analyses.
authors.affiliation: Laboratoire Suisse d'Analyse du Dopage, Institut Universitaire de Médecine Légale, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Chemin des Croisettes 22, 1066 Epalinges, Switzerland. christophe.saudan@chuv.ch
authors.forename: Christophe
authors.initials: C
authors.lastname: Saudan
authors.forename: Marc
authors.initials: M
authors.lastname: Augsburger
authors.forename: Patrice
authors.initials: P
authors.lastname: Mangin
authors.forename: Martial
authors.initials: M
authors.lastname: Saugy
mesh_terms: D002247:Carbon Isotopes / Q000032:analysis; D005554:Forensic Medicine / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D006885:Hydroxybutyrates / Q000493:pharmacokinetics / Q000652:urine*; D015203:Reproducibility of Results; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D002247:Carbon Isotopes; D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid