Measurement of exogenous gamma-hydroxybutyric acid (GHB) in urine using isotope ratio mass spectrometry (IRMS)

Aim: The objective of the study was to check if gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) is a suitable method to differentiate between endogenous and exogenous GHB in urine. Methods: In the presented study, a controlled and monitored administration of 2.25 g GHB (Xyrem) to one participant was carried out. Spot urine samples were collected once before administration and at different time intervals after the intake (2 h; 4 h; 6 h; 8 h; 12 h; 24 h; 48 h and 72 h). Concentrations of GHB were measured by LC/MS/MS and compared to carbon isotope ratios (CIR) analyzed by GC/C/IRMS. Results: The administered GHB was found to have a CIR of δCVPDB = -28.6 ± 0.1 ‰. For endogenous GHB prior to the administration a CIR of -23.7 ‰ was detected. After 6 hours the concentration of GHB was 4.2 μg/ml and therefore already below the accepted cut-off-value of 10 μg/ml. In comparison, the CIR was found to be -25.7 ‰, so an influence of the exogenous content could still be assumed after 6 hours. Conclusion: Due to its fast elimination, GHB intake in this study could not be demonstrated unambiguously for longer than 4 hours using LC/MS/MS as well as GC/C/IRMS.