The analysis and characterization of isomeric metabolites of temelastine by the combined use of thermospray liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry. 1989

T J Blake, and I G Beattie
Department of Drug Metabolism and Pharmacokinetics, Smith Kline & French Research Ltd, The Frythe, Welwyn, Herts, UK.

This paper describes the development and application of a combined thermospray liquid chromatographic/mass spectrometric and liquid chromatographic/tandem mass spectrometric method for distinguishing between five isomeric metabolites of Temelastine, comprising four hydroxylated metabolites and one N-oxide. The method allows the unambiguous characterization of all of the isomers either on their own or in the presence of each other. Clear results were obtained for the characterization of these metabolites in biological samples. Temelastine showed extensive phase I and phase II metabolism and the methodology was used to study the aglycone structures of the glucuronide conjugates derived from the hydroxylated metabolites. Photo-diode array ultraviolet spectroscopy was used as a complementary technique to help elucidate the site of glucuronidation in these species.

UI MeSH Term Description Entries
D007536 Isomerism The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Isomerisms
D011744 Pyrimidinones Heterocyclic compounds known as 2-pyrimidones (or 2-hydroxypyrimidines) and 4-pyrimidones (or 4-hydroxypyrimidines) with the general formula C4H4N2O. Pyrimidinone,Pyrimidone,Pyrimidones
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006900 Hydroxylation Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed) Hydroxylations
D013056 Spectrophotometry, Ultraviolet Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Ultraviolet Spectrophotometry
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass

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