Characterization of 2-amino-1-benzylbenzimidazole and its metabolites using tandem mass spectrometry.
We have investigated the in vitro hamster hepatic microsomal metabolism of the amino-azaheterocycle, 2-amino-1-benzylbenzimidazole (ABB). Three major metabolites were isolated and structurally characterized, using a combination of off-line HPLC, in conjunction with both electron ionization and fast atom bombardment ionization tandem mass spectrometry. ABB was shown to be debenzylated to afford 2-aminobenzimidazole (AB), as well as N- and C-oxidized to give 1-benzyl-N2-hydroxyaminobenzimidazole (BHB) and 2-amino-1-benzyl-hydroxybenzimidazole, respectively. The possible reasons for formation of the exocyclic hydroxylamine BHB are discussed. Furthermore, ABB is proposed as a suitable model compound for investigating parameters that control formation of toxic hydroxylamines derived from amino-azaheterocycles.
Ogunbiyi
O
O
Department of Pharmacy, King's College, University of London, UK.
Kajbaf
M
M
Lamb
J H
JH
Jahanshahi
M
M
Gorrod
J W
JW
Naylor
S
S
D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D006898:Hydroxylamines / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism*; D010087:Oxides / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment
D001562:Benzimidazoles; D006898:Hydroxylamines; D010087:Oxides; C094505:2-amino-1-benzylbenzimidazole