title: High-field asymmetric waveform ion mobility spectrometry for determining the location of in-source collision-induced dissociation in electrospray ionization mass spectrometry.
abstract: The understanding and control of the in-source collision-induced dissociation (CID) of analytes is important for the accurate LC-MS/MS quantitation of drugs and metabolites in biological samples. Accordingly, it was of interest to us to establish whether such in-source CID takes place after and/or before the orifice of an electrospray ionization (ESI) mass spectrometer. A high-field asymmetric waveform ion mobility spectrometry (FAIMS) system that is physically located between the sprayer and the orifice of a mass spectrometer can serve as an ion filter to control ions entering the orifice of the mass spectrometer. In such a configuration, FAIMS could conceivably be used to determine if the in-source CID of an analyte occurs after and/or before the mass spectrometer orifice. We demonstrated this capability of FAIMS using ifetroban acylglucuronide metabolite as a model compound. Under the conditions used, the results showed that the in-source CID conversion of the acylglucuronide metabolite to its parent drug ifetroban occurred almost entirely after the orifice of the mass spectrometer, with the conversion upstream of the orifice accounting for only 5.6% of the conversion. Under the circumstance, the term "post-orifice CID" rather than "in-source CID" may be more appropriate in describing such a dissociation occurring in the front end of a mass spectrometer.
authors.affiliation: Bioanalytical and Discovery Analytical Sciences, Research & Development, Bristol-Myers Squibb, Princeton, New Jersey 08543, USA.
authors.forename: Yuan-Qing
authors.initials: YQ
authors.lastname: Xia
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jemal
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis* / Q000378:metabolism; D020719:Glucuronides / Q000032:analysis* / Q000737:chemistry; D010080:Oxazoles / Q000032:analysis* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D020719:Glucuronides; D010080:Oxazoles; C078904:ifetroban