title: Molecular formula analysis by an MS/MS/MS technique to expedite dereplication of natural products.
abstract: A facile and sensitive mass spectrometric method has been developed for the dereplication of natural products. The method provides information about the molecular formula and substructure of a precursor molecule and its fragments, which are invaluable aids in dereplication of natural products at their early stages of purification and characterization. Collision-induced MS/MS technique is used to fragment a precursor ion into several product ions, and individual product ions are selected and subjected to collision-induced MS/MS/MS analysis. This method enables the identification of the fragmentation pathway of a precursor molecule from its first-generation fragments (MS/MS), through to the nth generation product ions (MSn). It also allows for the identification of the corresponding neutral products released (neutral losses). Elements used in the molecular formula analysis include C, H, N, O, and S, as most natural products are constituted by these five elements. High-resolution mass separation and accurate mass measurements afforded the unique identification of molecular formula of small neutral products. Through sequential add-up of the molecular formulas of the small neutral products, the molecular formula of the precursor ion and its productions were uniquely determined. The molecular formula of the precursor molecule was then reversely used to identify or confirm the molecular formula of the neutral products and that of the productions. The molecular formula of the neutral fragments allowed for the identification of substructures, leading to a rapid and efficient characterization of precursor natural product. The method was applied to paclitaxel (C47H51NO14; 853 amu) to identify its molecular formula and its substructures, and to characterize its potential fragmentation pathways. The method was further validated by correctly identifying the molecular formula of minocycline (C23H27N3O7; 457 amu) and piperacillin (C23H27N5O7S; 517 amu).
authors.affiliation: Biotechnology Research Institute, National Research Council Canada, 6100 Royalmount Avenue, Montréal, Québec, Canada H4P 2R2. yasuo.konishi@cnrc-nrc.gc.ca
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Konishi
authors.forename: Taira
authors.initials: T
authors.lastname: Kiyota
authors.forename: Cristina
authors.initials: C
authors.lastname: Draghici
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Gao
authors.forename: Faustinus
authors.initials: F
authors.lastname: Yeboah
authors.forename: Stephane
authors.initials: S
authors.lastname: Acoca
authors.forename: Suwatchai
authors.initials: S
authors.lastname: Jarussophon
authors.forename: Enrico
authors.initials: E
authors.lastname: Purisima
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D004602:Elements; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001688:Biological Products; D004602:Elements