IDENTIFICATION OF RAT FECAL METABOLITES OF EBASTINE BY B E LINKED SCANNING LIQUID SECONDARY-ION MASS-SPECTROMETRY/

The identification of rat faecal metabolites of a new antihistaminic a gent, ebastine, 4'-tert-butyl-4-[4(diphenylmethoxy)piperidino] butyrop henone, is presented. After oral administration of (C-14)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 th eir structures were identified by liquid secondary ion mass spectromet ry using the BIE linked scanning technique. The main metabolic pathway s were oxidation of a terminal methyl group to give the hydroxymethyl and carboxyl derivatives, and hydroxylation of a phenyl ring in the di phenylmethoxy moiety. In addition to the oxidative mechanism, metaboli sm of ebastine involved sulphate conjugation. It is noteworthy that M- 4, having both phenolic and alcoholic hydroxyl groups, was sulphated s electively in the latter position.