ABSTRACT
A novel metabolite, alpha-phenyl-gamma-butyrolactone, isolated from the urine of a glutethimide overdose victim, was synthesized and tested for biological activity in mice. Interperitoneal injections of this lactone caused severe toxicity at moderate dose levels. These results point to another metabolite of glutethimide contributing toxicity to patients severely intoxicated by the parent drug. An improved synthesis as well as complete spectral data of this lactone are also presented.
Subject(s)
4-Butyrolactone/toxicity , Furans/toxicity , Glutethimide/metabolism , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/urine , Animals , Chromatography, Gas , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Spectrophotometry, InfraredABSTRACT
A novel metabolite, alpha-phenyl-gamma-butyfolactone has been isolated in urine samples of patients severely intoxicated by either glutethimide, phenobarbital, or primidone. This lactone was prepared synthetically and its spectral data and chromatographic properties were compared to those data obtained from the urine samples of drug overdosed victims. The results of these comparisons confirm the presence of this lactone in human urine following the ingestion of large amounts of the parent drug.
Subject(s)
Glutethimide/metabolism , Phenobarbital/metabolism , Primidone/metabolism , Glutethimide/poisoning , Humans , Phenobarbital/poisoning , Primidone/poisoningABSTRACT
A metabolite of glutethimide, 2-ethyl-2-(3,4-dihydroxyphenyl)-glutarimide, previously identified in enzymatically hydrolyzed human urine of overdosed victims was prepared synthetically and its chemical and spectral data compared to the proposed material. Results of these comparisons confirm the presence of a catechol metabolite of glutethimide in the urine of patients severely intoxicated by the parent drug.
Subject(s)
Catechols/urine , Glutethimide/analogs & derivatives , Catechols/chemical synthesis , Chromatography, Gas , Glutethimide/urine , Humans , Mass SpectrometryABSTRACT
A new metabolite of glutethimide has been isolated and identified as a methylated catechol. Gas chromatographic parameters as well as mass spectral data are presented which clearly reveal this metabolite to be present in enzymatically hydrolyzed urine of patients severely intoxicated by the parent drug.
Subject(s)
Catechols/metabolism , Glutethimide/urine , Chemical Phenomena , Chemistry , Glutethimide/analogs & derivatives , HumansABSTRACT
The compound, 2-ethyl-2-(4-hydroxyphenyl)-glutarimide was prepared synthetically. Spectral data is presented which identifies this compound to be a metabolite of glutethimide isolated from enzymatically hydrolyzed human urine, following an overdose of the parent drug. New data supporting the structure of a minor metabolite, 2-ethyl-2-(3-methoxy-4-hydroxy)-glutarimide, is considered. Finally, gas chromatographic techniques have been perfected and are presented which yield complete purification of new metabolites of glutethimide.
Subject(s)
Glutethimide/analogs & derivatives , Chromatography, Gas , Chromatography, Thin Layer , Glutethimide/chemical synthesis , Glutethimide/urine , Humans , Magnetic Resonance Spectroscopy , Mass SpectrometryABSTRACT
Urine samples from comatose patients, identified as having taken large amounts of the drug, glutethimide, were analyzed using gas chromatography, mass spectrometry, thin layer chromatography, and nuclear magnetic resonance spectrometry in order to identify metabolites of the parent drug. The phenolic compound 2-ethyl-2-(4-hydroxphenyl)-glutarimide was fully characterized as a new metabolite in human urine. Also 2-ethyl-2-(3-methoxy-4hydroxyphenyl)-glutarimide was proposed as a new metabolite of the parent drug. Other polar metabolites of the parent drug were also detected and partially characterized.
