GLC Determination of Propranolol, Other β-Blocking Drugs, and Metabolites in Biological Fluids and Tissues

Abstract

A highly sensitive and specific electron-capture GLC method was developed for β-blocking drugs, including propranolol, Oxprenolol, alprenolol, pronethalol, dichloroisoproterenol, practolol, and Sotalol, and several of their metabolites. The drugs are separated and detected as their trifluoroacetyl derivatives. Minimum detectable amounts ranged from 0.1 to 1.1 pg. The chemical structures of the derivatives were confirmed by GLC-mass spectrometry. Propranolol was extracted from plasma by either a single- or a back-extraction procedure, with Oxprenolol as the internal standard. The minimum detectable concentration was 0.1 ng/ml plasma. The standard curve was linear from 0.5 to 500 ng/ml. Applications of this method demonstrated quantitatively detectable plasma propranolol levels 24 hr after a small (0.05 mg/kg) intravenous dose. Accurate plasma determinations could be made in patients receiving numerous other drugs. The method was shown to be applicable to propranolol and two metabolites, l-(α-naphthoxy)-2,3- propylene glycol and N-desisopropylpropranolol, in tissue. Determinations of picogram amounts of Oxprenolol and its four major urinary metabolites demonstrate the general applicability of the method to all 0-blocking drugs and most of their metabolites.Keyphrases: Propranolol and two metabolites–GLC determination in biological fluids and tissues; β-Blocking drugs–electron-capture GLC determination of propranolol, oxprenoiol, alprenolol, pronethalol, dichloroisoproterenol, practolol, Sotalol, and several metabolites in biological fluids and tissues; GLC–determination of propranolol, other β-blocking drugs, and metabolites in biological fluids and tissues