Gas-chromatographic simultaneous analysis for glutethimide and an active hydroxylated metabolite in tissues, plasma, and urine.

We report a gas-chromatographic method for the simultaneous quantitative analysis of both glutethimide and 4-hydroxy-2-ethyl-2-phenylglutarimide (4HG), an active metabolite of glutethimide, in tissues, plasma, and urine. The method, applied to postmortem tissues from cases of fatal glutethimide overdose and to plasma samples obtained from a patient in coma from acute glutethimide intoxication, proved to be accurate, sensitive, and specific. Results of the analysis confirm that 4-HG accumulates in plasma and tissues during glutethimide intoxication. Because 4-HG has been shown previously to be at least as potent as glutethimide itself, its accumulation may play an important role in the acute toxicity of glutethimide.