QUANTITATIVE MAPPING OF METABOLITES OF IMIPRAMINE AND DESIPRAMINE IN PLASMA SAMPLES BY GAS CHROMATOGRAPHIC-MASS SPECTROMETRY

  • 1 January 1981
    • journal article
    • research article
    • Vol. 16  (10) , 937-944
Abstract
Imipramine and desipramine are metabolized primarily by demethylation and hydroxylation. Hydroxy metabolites, 2-hydroxyimipramine and 2-hydroxydesipramine, are reported to be pharmacologically active by in vitro studies. A simple gas chromatographic-mass spectrometric (GC-MS) selected ion-monitoring (SIM) method is reported for hydroxy metabolites of imipramine and desipramine from plasma samples using deuterated analogs as internal standards. d4-Internal standards for imipramine, desipramine and their 2-hydroxy derivatives were prepared and added to plasma samples, extracted at pH 9 with ethyl acetate, then at pH > 11 with hexane-isopropanol. The extracts were combined and evaporated under nitrogen. The trifluoroacetyl derivatives were prepared using N-methyl-bis-trifluoroacetamide and analyses were performed using GC-MS selected ion-monitoring in the electron ionization mode. Hydroxylation to 2-hydroxy metabolites varied widely between [human] subjects. In vivo methylation of desipramine to imipramine as a pathway of its metabolism was noticed in 15% of the subjects. Plasma levels of all active metabolites must be considered in the assessment of the relationship of plasma levels of the drug to clinical response.

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