RT Journal Article
SR Electronic
T1 Comparative metabolism of four allylic barbiturates and hexobarbital by the rat and guinea pig.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 527
OP 546
VO 5
IS 6
A1 D J Harvey
A1 L Glazener
A1 D B Johnson
A1 C M Butler
A1 M G Horning
YR 1977
UL http://dmd.aspetjournals.org/content/5/6/527.abstract
AB A method for the extraction and identification of urinary metabolites of allylic barbiturates by gas chromatography and mass spectrometry is described. The metabolites from rat and guinea pig urine were extracted and separated into two fractions (an acidic and a nonacidic fraction) by chromatography on DEAE-Sephadex before converted into suitable derivatives for gas phase analysis. N,N'-dimethyl derivatives were used except in cases where metabolic N-demethylation was possible, in which case N-ethylation yielded more information. Hydroxyl, keto, and epoxy groups were converted into trimethylsilyl (TMS), alkyloxime, and chloro-TMS derivatives, respectively. This procedure was used to identify metabolites present in urine at concentrations as low as 0.1 microgram/ml. The allyl sidechains of secobarbital, alphenal, allobarbital, and aprobarbital were metabolized to epoxides, diols, and, in the case of secobarbital, to a ketol. Other sidechains were usually hydroxylated. Secobarbital was metabolized to compounds containing hydroxyl groups in both chains. Hexobarbital was metabolized by allylic hydroxylation, and no evidence of the epoxide-diol pathway was observed. The significance of the detection of epoxides of the four allylic barbiturates is discussed.