GHB (γ-hydroxybutyric acid) is an endogenous neurotransmitter that binds to specific receptor, whose precise function remains unclear. It can also be considered a GABA (-aminobutyric acid, Figure 1b) derivative that readily cross the blood-brain barrier and is thus able to produce central nervous system (CNS) depression. Today GHB is used in clinical context to treat narcolepsy and alcoholism. In fact, its sedative and GABA-like activity can effectively suppress alcohol withdrawal syndrome symptoms; moreover, GHB also partially mimics alcohol effects on CNS, thus reducing craving and inhibiting the voluntary ethanol consumption. Aim of this study is the development of a reliable analytical method for the analysis of GHB in DBS (Dried Blood Spots) of alcohol-dependent patients undergoing treatment with the drug (Alcover®). DBS is a blood sampling technique where small volumes of blood are spotted and dried on a suitable filter paper. The dried samples can easily be shipped to an analytical laboratory and analysed. A capillary electrophoretic method with indirect UV detection was used, since GHB does not possess any chromophore chemical group. The migration times and the sensitivity were optimised by varying the dimensions of the capillary, the voltage and the composition of the Background Electrolyte (BGE). The DBS sample pre-treatment, based on protein precipitation, produces clean samples, devoid of any interfering endogenous compound. The preliminary assays on real DBS from alcohol-dependent patients gave satisfactory results. The method is currently undergoing validation for the purpose of demonstrating its applicability to Therapeutic Drug Monitoring (TDM).
Determination of GHB by Means of Capillary Electrophoresis with Indirect UV Detection
MORGANTI, EMANUELE;MANDRIOLI, ROBERTO;SARACINO, MARIA ADDOLORATA;RAGGI, MARIA AUGUSTA
2012
Abstract
GHB (γ-hydroxybutyric acid) is an endogenous neurotransmitter that binds to specific receptor, whose precise function remains unclear. It can also be considered a GABA (-aminobutyric acid, Figure 1b) derivative that readily cross the blood-brain barrier and is thus able to produce central nervous system (CNS) depression. Today GHB is used in clinical context to treat narcolepsy and alcoholism. In fact, its sedative and GABA-like activity can effectively suppress alcohol withdrawal syndrome symptoms; moreover, GHB also partially mimics alcohol effects on CNS, thus reducing craving and inhibiting the voluntary ethanol consumption. Aim of this study is the development of a reliable analytical method for the analysis of GHB in DBS (Dried Blood Spots) of alcohol-dependent patients undergoing treatment with the drug (Alcover®). DBS is a blood sampling technique where small volumes of blood are spotted and dried on a suitable filter paper. The dried samples can easily be shipped to an analytical laboratory and analysed. A capillary electrophoretic method with indirect UV detection was used, since GHB does not possess any chromophore chemical group. The migration times and the sensitivity were optimised by varying the dimensions of the capillary, the voltage and the composition of the Background Electrolyte (BGE). The DBS sample pre-treatment, based on protein precipitation, produces clean samples, devoid of any interfering endogenous compound. The preliminary assays on real DBS from alcohol-dependent patients gave satisfactory results. The method is currently undergoing validation for the purpose of demonstrating its applicability to Therapeutic Drug Monitoring (TDM).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
