Pathways of propranolol metabolism. Use of the stable isotope twin-ion GC-MS technique to examine the conversion of propranolol to propranolol-diol by 9000g rat liver supernatant.

The metabolic conversion of propranolol to propranolol-diol [1-(1-naphthyloxy)-2,3-propyleneglycol] by rat liver 9000g 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 loss of deuterium indicating that the possibility of rapidly tautomerizing imine intermediate did not make a significant contribution in this metabolic conversion. Desisopropylpropranolol, added in small amounts to the incubation 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 desisopropylpropranolol intermediate.