title: A systematic investigation of the fragmentation pattern of two furanoheliangolide C-8 stereoisomers using electrospray ionization mass spectrometry.
abstract: BACKGROUND
  Budlein A is a sesquiterpene lactone (STL) with some reported biological activities. Pre-clinical studies to identify in vivo metabolites often employ hyphenated techniques such as liquid chromatography/tandem mass spectrometry (LC/MS/MS). It is also possible to use the fragmentation pattern obtained by Collision-Induced Dissociation (CID) and Higher Energy Collision-Induced Dissociation (HCD) to distinguish between the stereoisomers budlein A and centratherin.
  
  
  METHODS
  The experiments were carried out in the positive mode using four different spectrometers with an electrospray ionization (ESI) source: (a) Waters ACQUITY(®) TQD triple quadrupole mass spectrometer (QqQ), (b) AB Sciex API 4000 QTrap(®) (QqQ), (c) Bruker Daltonics micrOTOF™-Q II (time-of-flight, QTOF), and (d) Thermo Scientific LTQ Orbitrap XL hybrid FTMS (Fourier transform mass spectrometer). Computational chemistry studies helped to identify the protonation sites. The B3LYP/6-31G(d) model furnished the equilibrium geometries and energies.
  
  
  RESULTS
  The stereochemistry (α- or β-orientation) of the centratherin and budlein A side-chain esters influences the fragmentation pattern recorded on QqQ, QTOF, and Orbitrap-HCD. On QqQ, centratherin releases the side chain, to generate the m/z 275 fragment ion, whereas budlein A gives the m/z 83 fragment ion. On QTOF and Orbitrap-HCD, only budlein A affords the m/z 293 and 83 fragment ions, respectively.
  
  
  CONCLUSIONS
  The data suggest that proton migration governs the fragmentation pathways under α- or β-orientation. The difference in the QqQ, QTOF, and Orbitrap-HCD spectral profiles of each isomer can help to distinguish between centratherin and budlein A using MS/MS, which becomes an alternative to nuclear magnetic resonance (NMR) analysis.
authors.affiliation: Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS) - Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil; Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, 48149, Münster, Germany.
authors.forename: Lucas Rossi
authors.initials: LR
authors.lastname: Sartori
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vessecchi
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.forename: Fernando Batista
authors.initials: FB
authors.lastname: Da Costa
authors.forename: Norberto Peporine
authors.initials: NP
authors.lastname: Lopes
mesh_terms: D001952:Bridged-Ring Compounds / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D007477:Ions / Q000032:analysis / Q000737:chemistry; D007783:Lactones / Q000032:analysis / Q000737:chemistry*; D012717:Sesquiterpenes / Q000032:analysis / Q000737:chemistry*; D054830:Sesterterpenes; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D001952:Bridged-Ring Compounds; D005663:Furans; D007477:Ions; D007783:Lactones; D012717:Sesquiterpenes; D054830:Sesterterpenes; C520233:budlein A; C442701:centratherin; C499803:furanoheliangolide