Study of the metabolites of bencycloquidium bromide racemate, a novel anticholinergic compound, in rat bile by liquid chromatography-tandem mass spectrometry

A sensitive and specific liquid chromatographic-electrospray ionization (ESI) tandem ion trap mass spectrometric method has been developed for identification of bencycloquidium bromide (BCQB) and its metabolites in rat bile. Six healthy rats were administrated a single dose (3.0 mg kg(-1)) of BCQB by intraperitoneal (i.p.) injection. The bile were sampled from 0 h to 24 h and purified by using a C(18) solid- phase extraction (SPE) cartridge, then the purified bile samples were separated on a reversed-phase C(18) column using acetonitrile/40 mM ammonium acetate buffer (containing 0.1% formic acid) as mobile phase at gradient elution and detected by an on-line MS(n) detector. Identification and structural elucidation of the metabolites were performed by comparing the changes in molecular weight (Deltam) and full scan MS(n) spectra with those of the parent drug. Eight metabolites (such as hydroxylated and oxidized metabolites) and the parent drug were found in rat bile. Eight metabolites of BCQB were identified and hydroxylated metabolites were the major metabolites. The metabolic pathways of BCQB in vivo are proposed for the first time.