PATHWAYS OF PROPRANOLOL METABOLISM - USE OF STABLE ISOTOPE TWIN-ION GC-MS TECHNIQUE TO EXAMINE CONVERSION OF PROPRANOLOL TO PROPRANOLOL-DIOL BY 9000G RAT-LIVER SUPERNATANT

  • 1 January 1978
    • journal article
    • research article
    • Vol. 21  (1) , 77-85
Abstract
The metabolic conversion of propranolol to propranolol-diol [1-(1-naphthyloxy)-2,3-propyleneglycol] by rat liver 9000 g supernatant was demonstrated to proceed through the intermediate 3-naphthyloxy-2-hydroxypropionaldehyde. Using side chain deuterated propranolol-d5, as substrate, propranolol-diol-d4 was produced, indicating an obligatory aldehyde intermediate. Analysis of desisopropylpropranolol obtained in the same incubation showed no less of deuterium, indicating that the possibility of rapidly tautomerizing imine intermediates did not make significant contribution in this metabolic converwion. Desisopropylpropranolol, added in small amounts to the indubation mixture is more rapidly converted to the propranolol-diol than is propranolol, indicating that the major pathway of conversion of propranolol to its diol metabolite is through the desisopropyl-propranolol intermediate.