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Rapid identification of cimetropium bromide metabolites using constant neutral loss tandem mass spectrometry
Author(s) -
Naylor S.,
Kajbaf M.,
Lamb J. H.,
Jahanshahi M.,
Gorrod J. W.
Publication year - 1992
Publication title -
biological mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1052-9306
DOI - 10.1002/bms.1200210309
Subject(s) - chemistry , mass spectrometry , tandem mass spectrometry , fast atom bombardment , chromatography , ion , fragmentation (computing) , bromide , mass spectrum , solid phase extraction , analytical chemistry (journal) , inorganic chemistry , organic chemistry , computer science , operating system
A combination of constant neutral loss (CNL) and daughter ion scanning tandem mass spectrometry was used to identify nine metabolites of the antimuscarinic drug cimetropium bromide. CNL mass spectrometry (‐54 Da, corresponding to loss of ‐CH 2 ‐cyclopropyl with a concomitant gain of H) was used to rapidly screen an extract from a rat liver microsomal incubate. This sample had been subjected to only minimal purification involving zinc sulphate precipitation of the microsomal proteins followed by solid‐phase extraction using a Sep‐Pak C‐18 reversed‐phase cartridge. The ions detected in CNL mass spectrometry were subjected to collisionally activated dissociation and the resulting daughter ion spectra were compared with those acquired for synthetic standards. Four ions observed in CNL mass spectrometry were shown to be artifacts, produced either by the fast atom bombardment (FAB) ionization process or the incubation and/or extraction conditions. Their structures were determined from the daughter ion spectra acquired. It was also demonstrated that in the presence of high concentrations of the unmetabolized drug substrate, ions were formed during FAB ionization that possessed identical daughter ion spectra to previously identified metabolites. This observation highlighted the need to conduct adequate control experiments to ensure that artifacts from the FAB process, as well as from the incubation procedures, were distinguished from ions attributable to metabolites.