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

Abstract

Rationale: γ-Hydroxybutyric acid (GHB) is a naturally endogenous neurotransmitter that is popular as a recreational drug due to its sedative, hypnotic, and euphoric effects. GHB derived from endogenous production or exogenous ingestion has been effectively discriminated by carbon isotopic compositions (δ13C values) through gas chromatography/combustion-isotope ratio mass spectrometry (GC/C-IRMS). However, an unintended uncertainty of isotopic signatures caused by a wide range of GHB quantities remains unsolved when using only single-isotope corrections of the di-TMS derivative. Methods: The δ13C values of the original GHB standard were first determined by elemental analyzer/isotope ratio mass spectrometry (EA/IRMS). The δ13C values of silylated GHB in concentrations from 10 to 500 ppm were determined by GC/C-IRMS. With respect to the silylated reaction products, the correction of δ13C values for the introduced carbons was calculated from a stoichiometric mass balance equation. Results: The results showed a significant quantity-dependent trend in δ13C values of introduced carbon (δ13Cdi-TMS values) with increased GHB standard concentrations (r2 = 0.70, p <0.05). We applied a logarithmic equation to determine isotopic data in low-GHB urine specimens from five healthy female volunteers. The δ13CGHB values in urine samples corrected with quantity-dependent δ13Cdi-TMS values were different by an average of 2.7‰ from those corrected with single δ13Cdi-TMS values (p [removed]