Use of high-performance liquid chromatography-thermospray mass spectrometry and gas chromatography-electron-impact mass spectrometry in the identification of the metabolites of alpha-methylacetohydroxamic acids, potential anti-asthmatic agents.
Two potential anti-asthmatic alpha-methylacetohydroxamic acids, compound 1 and compound II were metabolised to two major products (metabolite 1 and metabolite 2) after oral dosing to rabbits. Metabolite 1, extracted under acid conditions from the plasma and urine of dosed animals, was identified as a glucuronide by incubation with beta-glucuronidase and subsequent high-performance liquid chromatographic-mass spectrometric (HPLC-MS) analysis of the aglycone. HPLC-MS analysis of metabolite 2 suggested that it was the acetamide, however, unequivocal identification was obtained by further analysis using gas chromatography-mass spectrometry (GC-MS) of its trimethylsilyl derivative and by comparison with the mass spectra of the authentic acetamides. This study shows the advantages of combining HPLC-MS with other techniques such as GC-MS for the identification of metabolites.
Woollard
P M
PM
Wellcome Research Laboratories, Beckenham, Kent, U.K.
Salmon
J A
JA
Padfield
A D
AD
D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D044482:Benzeneacetamides; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006868:Hydrolysis; D006877:Hydroxamic Acids / Q000032:analysis* / Q000378:metabolism; D010647:Phenyl Ethers / Q000032:analysis* / Q000378:metabolism; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014297:Trimethylsilyl Compounds
D044482:Benzeneacetamides; D006877:Hydroxamic Acids; D010647:Phenyl Ethers; D014297:Trimethylsilyl Compounds; C068763:BW A879C; C068762:BW B218C; C047270:N,N-bis(trimethylsilyl)-2,2,2-trifluoroacetamide