Simultaneous determination of blood concentrations of methohexital and its hydroxy metabolite by gas chromatography and identification of 4'-hydroxymethohexital by combined gas--liquid chromatography--mass spectrometry.

A simple, sensitive and selective method is described for the simultaneous determination of low concentrations (less than 50 ng/ml) of underivatized methohexital and its hydroxy metabolite in small (0.1 ml) samples of human and rat plasma or whole blood by gas chromatography with nitrogen-selective detection. Moreover, the main metabolite in rat and man was identified as 4'-hydroxymethohexital by comparison of chromatograms from gas--liquid chromatography (GLC) with data obtained from GLC--mass spectrometry and 1H-nuclear magnetic resonance spectrometry of this metabolite, produced both by incubating methohexital with isolated rat liver microsomes and by isolating this metabolite from rat urine.