Metabolism of the mutagen MeIQx in vivo: metabolite screening by liquid chromatography-thermospray mass spectrometry.
2-Amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) is a potent mutagen found in cooked food. MeIQx and its isotopically labelled (13C, 15N2 and 14C) analogues were synthesised and used for metabolic studies in vivo. An equimolar mixture of MeIQx and its 13C, 15N2 stable isotope labelled analogue (containing tracer amounts of 14C-MeIQx) was given intraperitoneally to mice. Some 67% of the radioactivity was eliminated in urine and faeces within 24h. Four radiolabelled species were observed when urine was analysed by HPLC, corresponding to unchanged MeIQx and three more polar metabolites. Urine was analysed directly by HPLC-thermospray mass spectrometry. Four signals were observed containing the characteristic 1:1 isotopic doublet, corresponding to unchanged MeIQx, an MeIQx glucuronide, and two uncharacterized metabolites.
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
N J
NJ
Gooderham
D
D
Watson
J C
JC
Rice
S
S
Murray
G W
GW
Taylor
D S
DS
Davies
D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D051379:Mice; D011810:Quinoxalines / Q000378:metabolism* / Q000493:pharmacokinetics
D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline