title: Using electron induced dissociation (EID) on an LC time-scale to characterize a mixture of analogous small organic molecules.
abstract: LC ESI FTICR MS of a sample of cediranib identified this pharmaceutical target molecule plus an additional 10 compounds of interest, all of which were less than 10% total ion current (TIC) peak intensity relative to cediranib. LC FTICR tandem mass spectrometry using electron induced dissociation (EID) has been achieved and has proven to be the best way to generate useful product ion information for all of these singly protonated molecules. Cediranib [M + H](+) fragmented by EID to give 29 product ions whereas QTOF-CID generated only one very intense product ion, and linear ion trap-CID, which generated 10 product ions, but all with poor S/N. Twenty-six of the EID product ions were unique to this fragmentation technique alone. By considering the complementary LC-EID and LC-CID data together, all 10 unknown compounds were structurally characterized and proven to be analogous to cediranib. Of particular importance, EID produced unique product ion information for one of the low level cediranib analogues that enabled full characterization of the molecule such that the presence of an extra propylpyrrolidine group was discovered and proven to be located on the pyrrolidine ring of cediranib, solving an analytical problem that could not be solved by collision induced dissociation (CID). Thus, it has been demonstrated that EID is in harmony with the chromatography duty-cycle and the dynamic concentration range of synthetic compounds containing trace impurities, providing crucial analytical information that cannot be obtained by more traditional methodologies.
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
authors.forename: Aruna S
authors.initials: AS
authors.lastname: Prakash
authors.forename: Michael J P
authors.initials: MJ
authors.lastname: Smith
authors.forename: Zied
authors.initials: Z
authors.lastname: Kaabia
authors.forename: Glenn
authors.initials: G
authors.lastname: Hurst
authors.forename: Ci
authors.initials: C
authors.lastname: Yan
authors.forename: Martin
authors.initials: M
authors.lastname: Sims
authors.forename: Anthony W T
authors.initials: AW
authors.lastname: Bristow
authors.forename: Peter
authors.initials: P
authors.lastname: Stokes
authors.forename: David
authors.initials: D
authors.lastname: Parker
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Mosely
mesh_terms: D002625:Chemistry, Organic / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D059629:Signal-To-Noise Ratio; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations