Identification of rat faecal metabolites of ebastine by B/E linked scanning liquid secondary ion mass spectrometry.
The identification of rat faecal metabolites of a new antihistaminic agent, ebastine, 4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyrophenone, is presented. After oral administration of (14C)ebastine (20 mg kg-1) to rats, 84% of the radioactive dose was excreted in the 24 h faeces. Unchanged drug and five metabolites were isolated from the faeces by thin-layer chromatography and solid-phase extraction, and their structures were identified by liquid secondary ion mass spectrometry using the B/E linked scanning technique. The main metabolic pathways were oxidation of a terminal methyl group to give the hydroxymethyl and carboxyl derivatives, and hydroxylation of a phenyl ring in the diphenylmethoxy moiety. In addition to the oxidative mechanism, metabolism of ebastine involved sulphate conjugation. It is noteworthy that M-4, having both phenolic and alcoholic hydroxyl groups, was sulphated selectively in the latter position.
Yoshida
K
K
Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Hatoyama
T
T
Fujii
T
T
Kagemoto
A
A
Miyazaki
H
H
Naruto
S
S
D000818:Animals; D001711:Biotransformation; D002090:Butyrophenones / Q000032:analysis* / Q000493:pharmacokinetics; D002855:Chromatography, Thin Layer; D005243:Feces / Q000737:chemistry*; D006634:Histamine H1 Antagonists / Q000032:analysis* / Q000493:pharmacokinetics; D006868:Hydrolysis; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010880:Piperidines / Q000032:analysis* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000378:metabolism
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; D013431:Sulfates; C058249:ebastine