Premium
A selected ion monitoring method for glutethimide and six metabolites: Application to blood and urine from humans intoxicated with glutethimide
Author(s) -
Kennedy K. A.,
Ambre J. J.,
Fischer L. J.
Publication year - 1978
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200051209
Subject(s) - glutethimide , metabolite , urine , chemistry , chromatography , drug , active metabolite , pharmacology , medicine , biochemistry
Abstract 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, (1‐hydroxyethyl)glutethimide and p ‐hydroxyglutethimide. The unchanged drug, 3‐dehydroglutethimide, desethylglutethimide and the internal standard, [ 2 H 5 ]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 μg ml −1 ) 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 μg ml −1 ). The major urinary metabolites were conjugates of 4‐hydroxyglutethimide and (1‐hydroxyethyl)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 unchanged drug and unconjugated metabolites indicated that drug elimination was not markedly impaired in the intoxicated patients.