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Phase I metabolites (organic acids) of gamma-hydroxybutyric acid -validated quantification by GC-MS and description of endogenous concentration ranges.

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Gamma hydroxybutyric acid (GHB) is known as a sedative drug used in Drug Facilitated Crimes. Its detection window is very short. GHB undergoes intensive phase I metabolism to organic acids… Click to show full abstract

Gamma hydroxybutyric acid (GHB) is known as a sedative drug used in Drug Facilitated Crimes. Its detection window is very short. GHB undergoes intensive phase I metabolism to organic acids (glycolic acid, succinic acid, dihydroxy butyric acids). These could be potential analytical targets to broaden the detection window. The aim of the present study was to enable the detection of endogenous levels of these metabolites in biological samples (blood and urine). A gas chromatographic mass spectrometric method using liquid liquid extraction and derivatization wth MSTFA for the quantification was developed. Validation results were in accordance with international guidelines and the method was able to quantify endogenous levels of the substances in both urine and blood. Endogenous concentrations were shown to be < 0.03-4.92 mg/L for glycolic acid, < 0.03 to 1.28 mg/L for GHB, < 0.28-18.1 mg/L for succinic acid, < 0.12-1.38 mg/L for 2,4-dihydroxy butyric acid and < 0.13-2.59 mg/L for 3,4-dihydroxy butyric acid, respectively, in serum samples of 101 volunteers. Urinary endogenous concentrations were shown to be 1.30-400 mg/L for glycolic acid, < 0.03 to 1.94 mg/L for GHB, 1.17-273 mg/L for succinic acid, 0.72-26.2 mg/L for 2,4-dihydroxy butyric acid and 1.88 - 122 mg/L for 3,4-dihydroxy butyric acid, respectively, in urine samples of 132 volunteers. These endogenous concentrations represent a basis to which concentrations after the intake of GHB can be compared to in order to proof the intake of this substance.

Keywords: gamma hydroxybutyric; hydroxybutyric acid; dihydroxy butyric; acid; organic acids

Journal Title: Drug testing and analysis
Year Published: 2020

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