The modification of a procedure originally developed for the analysis of ethylene glycol (EG) in serum was also found to permit the simultaneous analysis of gamma-hydroxybutyrate (GHB) in whole blood. The primary feature of the EG procedure was that it employed a water scavenger, 2,2-dimethoxypropane, which reacted with water to produce volatile methanol. Water scavenging is a technique that could be adapted for the analysis of drugs such as GHB as their respective di-t-butyldimethylsilyl derivatives. A close structural analogue of GHB, 2-hydroxy-3-methylbutyric acid, was successfully employed as the internal standard for both EG and GHB. The advantages of the modified procedure are that it is very quick and easy to perform and produces remarkably clean extracts for GHB, especially when compared to other liquid-liquid techniques. We have successfully applied this technique for the analysis of GHB and EG in several postmortem and driving-under-the-influence cases. There is an apparently wide variability between levels of GHB that can be associated with impairment versus those levels that can be associated with death.
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