Study of the metabolic pathways of alprenolol in man and the dog using stable isotopes

Hoffmann, Kurt‐Jürgen; Arfwidsson, A.; Borg, K. O.; Skånberg, Inger

doi:10.1002/bms.1200051108

Cited by 19 publications

(2 citation statements)

References 15 publications

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“…The chlorine in these derivatives tends to be labile and can abstract a proton to eliminate HCl. Such a reaction is seen in derivatives of the oral anti‐rheumatic drug RS‐2‐(4‐ iso ‐butylphenyl)propionic acid (“ibuprofen”) (Brooks & Gilbert, ) and the β‐blockers, propranolol ( 230 ) (Hammar, ) and alprenolol (Hoffmann et al, ) and a variety of others (Black et al, ). In the case of the β‐blockers, a cyclization reaction occurred such that the derivative was in fact a cyclic compound ( 231 , shown for propranolol, Scheme ) having lost the chlorine atom from the derivative and a hydrogen from the drug's nitrogen.…”

Section: Other Silyl Derivativesmentioning

confidence: 99%

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Harvey

Vouros

2019

Mass Spectrometry Reviews

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This review describes the mass spectral fragmentation of trimethylsilyl (TMS) and related alkylsilyl derivatives used for preparing samples for analysis, mainly by combined gas chromatography and mass spectrometry (GC/MS). The review is divided into three sections. The first section is concerned with the TMS derivatives themselves and describes fragmentation of derivatized alcohols, thiols, amines, ketones, carboxylic acids and bifunctional compounds such as hydroxy‐ and amino‐acids, halo acids and hydroxy ethers. More complex compounds such as glycerides, sphingolipids, carbohydrates, organic phosphates, phosphonates, steroids, vitamin D, cannabinoids, and prostaglandins are discussed next. The second section describes intermolecular reactions of siliconium ions such as the TMS cation and the third section discusses other alkylsilyl derivatives. Among these latter compounds are di‐ and trialkyl‐silyl derivatives, various substituted‐alkyldimethylsilyl derivatives such as the tert‐butyldimethylsilyl ethers, cyclic silyl derivatives, alkoxysilyl derivatives, and 3‐pyridylmethyldimethylsilyl esters used for double bond location in fatty acid spectra. © 2019 Wiley Periodicals, Inc. Mass Spec Rev 0000:1–107, 2019

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Section: Other Silyl Derivativesmentioning

confidence: 99%

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Harvey

Vouros

2019

Mass Spectrometry Reviews

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“…Metabolite H 117/67 is a lactic acid derivative and its molecular weight of 393 is consistent with the structure depicted in figure 6. The base peak m/e 199 and fragment m/e 171 are characteristic for the derivatized lactic acid moiety, as reported for the corresponding acidic metabolite of alprenolol (4). According to the mass spectrum, either the carbamate function does not form a derivative with TFA-anhydride or this TFA group is readily eliminated under electron impact ionization.…”

Section: Acidic Metabolite H 117/67mentioning

confidence: 83%

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

Hoffmann¹,

Skånberg²,

Borg³

1979

European Journal of Drug Metabolism and Pharmacokinetics

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The metabolism of pamatolol was studied in man, dogs, rats and mice after oral administration of a single dose. The drug was well absorbed in the gastro-intestinal tract and excreted in the urine, mainly in unchanged form, within 24 hrs. Four urinary metabolites were identified by gas chromatographic-mass spectrometric techniques. The metabolic data, in man, dog and mouse was found to be similar, both qualitatively and quantitatively. One metabolism route, involving aliphatic hydroxylation and subsequent oxidation, was found, to a significant extent only in the rat. The species variation between the mouse and the rat with regard to long-term toxicity of pamatolol is discussed. Artefact formation during trace analysis was observed.

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Propranolol, alprenolol and oxprenolol metabolism in the dog. Identification ofN-Methylated metabolites

Walle

Wilson

Walle

1981

Biol. Mass Spectrom.

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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.

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Study of the metabolic pathways of alprenolol in man and the dog using stable isotopes

Cited by 19 publications

References 15 publications

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

Propranolol, alprenolol and oxprenolol metabolism in the dog. Identification ofN-Methylated metabolites

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