Capillary electrophoresis with indirect UV detection for the Therapeutic Drug Monitoring (TDM) of GHB in human plasma

GHB (γ-hydroxybutyric acid) is an endogenous neurotransmitter that binds to specific receptor, whose precise function remains unclear. As a drug, it can also be considered as a GABA (γ-aminobutyric acid) derivative that can cross the blood-brain barrier and is thus able to produce central nervous system (CNS) depression. In the past, its main medical use has been that of coadjutant of intravenous anaesthetics, but it is now used to treat narcolepsy and, in some countries, alcohol dependence. In fact, its sedative and GABA-like activity can effectively suppress alcohol withdrawal syndrome symptoms; moreover, GHB also partially mimics the effects of alcohol on the CNS, thus reducing craving and inhibiting the drive to voluntary ethanol consumption. Aim of this study is the development of a reliable analytical method, based on capillary electrophoresis, for the analysis of GHB in the plasma of alcohol-dependent patients undergoing treatment with the drug (Alcover®). Since the analyte does not possess any chromophore, its detection can be problematic; instead of complicate and time-consuming derivatisation procedures, an indirect UV detection system was used to obtain the necessary sensitivity. The plasma sample pre-treatment, based on protein precipitation, produces clean samples devoid of any interfering endogenous compound. The first few assays on real patient plasma samples gave satisfactory results. The method is currently undergoing validation for the purpose of demonstrating its applicability to therapeutic drug monitoring (TDM).