title: Analysis of alpha-hydroxy metabolites of metoprolol in human urine after phosgene/trimethylsilyl derivatization.
abstract: Three metoprolol metabolites containing an alpha-hydroxy group were identified in human urine by capillary column gas chromatography/mass spectrometry. After aqueous phase cyclization with phosgene the neutral or acidic derivatives formed were isolated by solvent extraction at pH 10 or 3, respectively. Following silylation the electron impact mass spectra of the metabolites exhibited a characteristic ion at m/z 336 of high abundance which originated from cleavage of the bond adjacent to the alpha-OTMS group. Most probably the identified compounds were formed by further biotransformations of alpha-hydroxy metoprolol, which is a primary metabolite. The analytical method is applicable to detect the metoprolol metabolites reported so far. A quantitative assay for one of the metabolites (H 119/72) with nitrogen selective detection is described. The total amount of this metabolite excreted by one subject within 24 h after dosing was about 0.25% of the given dose.
mesh_terms: D002849:Chromatography, Gas; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007202:Indicators and Reagents; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000652:urine; D010705:Phosgene; D014297:Trimethylsilyl Compounds
chemical_list: D007202:Indicators and Reagents; D014297:Trimethylsilyl Compounds; D010705:Phosgene; C029504:alpha-hydroxymetoprolol; D008790:Metoprolol