A selected ion monitoring method for glutethimide and six metabolites: Application to blood and urine from humans intoxicated with glutethimide
✍ Scribed by K. A. Kennedy; J. J. Ambre; L. J. Fischer
- Publisher
- John Wiley and Sons
- Year
- 1978
- Tongue
- English
- Weight
- 725 KB
- Volume
- 5
- Category
- Article
- ISSN
- 1076-5174
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✦ Synopsis
A method employing selected ion monitoring for the analysis of glutethimide and six of its metabolites has been developed. Hydroxylated metabolites analyzed as trifluoroacetates, included 4-hydroxyglutethimide, (l-hydr-oxyethy1)glutethhde and p-hydroxyglutethimide. The unchanged drug, 3-dehydroglutethimide, desethylglutethimide and the internal standard, [2H5]glutethimide, were chromatographed underivatized on OV-225.
The assay was used to measure drug and metabolites in the plasma and urine of patients intoxicated with glutethimide. High levels (e.g. 20-35 p g d -' ) of unconjugated 4-hydroxyglutethimide, an active metabolite, were found in all patients at a time when levels of unchanged drug were lower and declining. Other unconjugated and conjugated metabolites were found in relatively low concentrations in the plasma (i.e. <4 eg d -' ) . The major urinary metabolites were conjugates of 4-hydroxyglutethimide and (1-hydroxyethy1)glutethimide. The unchanged drug and other conjugated and unconjugated metabolites were found in lower amounts in the urine. Normal plasma half-lives of glutethimide and the relatively small amounts in urine of unchrtnged h g and unconjugated metabolites indicated that drug elimination was not markedly impaired in the intoxicated patients.