Liquid Extraction Surface Analysis (LESA) Electron-Induced Dissociation and Collision-Induced Dissociation Mass Spectrometry of Small Molecule Drug Compounds

Research output: Contribution to journalArticle

Colleges, School and Institutes

External organisations

  • School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
  • Pathology, Drug Safety & Metabolism, IMED Biotech Unit, AstraZeneca, Darwin Building, Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK.
  • School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. h.j.cooper@bham.ac.uk.

Abstract

Here, we present liquid extraction surface analysis (LESA) coupled with electron-induced dissociation (EID) mass spectrometry in a Fourier-transform ion cyclotron resonance mass spectrometer for the analysis of small organic pharmaceutical compounds directly from dosed tissue. First, the direct infusion electrospray ionisation EID and collision-induced dissociation (CID) behaviour of erlotinib, moxifloxacin, clozapine and olanzapine standards were compared. EID mass spectra were also compared with experimental or reference electron impact ionisation mass spectra. The results show that (with the exception of erlotinib) EID and CID result in complementary fragment ions. Subsequently, we performed LESA EID MS/MS and LESA CID MS/MS on singly charged ions of moxifloxacin and erlotinib extracted from a thin tissue section of rat kidney from a cassette-dosed animal. Both techniques provided structural information, with the majority of peaks observed for the drug standards also observed for the tissue-extracted species. Overall, these results demonstrate the feasibility of LESA EID MS/MS of drug compounds from dosed tissue and extend the number of molecular structures for which EID behaviour has been determined. Graphical Abstract ᅟ.

Details

Original languageEnglish
Pages (from-to)2218-2226
Number of pages9
JournalJournal of the American Society for Mass Spectrometry
Volume29
Issue number11
Early online date27 Aug 2018
Publication statusPublished - Nov 2018

Keywords

  • CID, Collision-induced dissociation, Drug compounds, EI, EID, Electron ionisation, Electron-induced dissociation, LESA, Liquid extraction surface analysis, Small molecules dissociation