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.
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.
Blake
T J
TJ
Department of Drug Metabolism and Pharmacokinetics, Smith Kline & French Research Ltd, The Frythe, Welwyn, Herts, UK.
Beattie
I G
IG
D002853:Chromatography, Liquid; D005243:Feces / Q000032:analysis; D005965:Glucuronates / Q000032:analysis; D006801:Humans; D006900:Hydroxylation; D007536:Isomerism; D013058:Mass Spectrometry; D011744:Pyrimidinones / Q000032:analysis* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D005965:Glucuronates; D011744:Pyrimidinones; C049054:temelastine