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Propranolol, alprenolol and oxprenolol metabolism in the dog. Identification of N ‐Methylated metabolites
Author(s) -
Walle U. Kristina,
Wilson Michael J.,
Walle Thomas
Publication year - 1981
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200080206
Subject(s) - alprenolol , chemistry , oxprenolol , metabolism , propranolol , chromatography , mephenytoin , glucuronic acid , metabolic pathway , biochemistry , endocrinology , biology , polysaccharide , cytochrome p450 , cyp2c19 , receptor
The metabolism of propranolol, alprenolol and oxprenolol was studied in the dog and rat; propranolol in five additional species, including man. Basic, phenolic and neutral metabolites were extracted from urine at pH 9.6 after enzymatic hydrolysis. Separation and identification of parent drug and seven metabolites each for propranolol, alprenolol and oxprenolol in the dog were accomplished by gas chromatography mass spectrometry as the trifluoroacetyl derivatives. A very uniform and predictable fragmentation pattern was observed for all 24 compounds. Seven new metabolites were identified. The metabolism of all three drugs was qualitatively the same, including N ‐dealkylation followed by N ‐methylation or deamination of the primary amines. The parent drugs as well as all of their sidechain metabolism products were also partially ring hydroxylated. N ‐Methylation was only found in the dog and is a minor metabolic pathway. The stereochemical composition of N ‐methyldesisopropylpropranolol and its immediate precursor N ‐desisopropylpropranolol showed a marked enrichment of the (+)‐isomer.