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Abstract No.: TuP-081
Session: Drug Discovery and Development
Presentation date: Tue, Aug 29, 2006
Presentation time: 09:50 – 11:20

The Application of MALDI for Metabolites Identification in Biological Matrices

Lekha Sleno1,2, Emmanuel Varesio1,2, Yves LeBlanc3, Jean-Francois Alary3, Gerard Hopfgartner1,2

1 University of Geneva, Geneva, Switzerland
2 University of Lausanne, Lausanne, Switzerland
3 MDS Sciex, Toronto, Canada

Correspondence address: Emmanuel Varesio, University of Geneva, School of Phramaceutical Sciences, Life Sciences Mass Spectrometry, 20 Bd d'Yvoy, Geneva, CH-1211 Switzerland.

Keywords: MALDI; Mass Spectrometry, Ion Trap Quadrupole; Mass Spectrometry, Quadrupole; Metabolism, Metabolites.

Novel aspect: Application of an experimental MALDI source on a triple quadrupole linear ion trap for drug metabolism.


Elucidation of the metabolism of new drug candidates is an essential part of the drug discovery and development process. Due to its high sensitivity and throughput capabilities mass spectrometry is an ideal technique for this kind of analysis. However, in order to find metabolites in complex matrices and characterize the structure of the metabolite, several MS experiments have often to be conducted. Liquid chromatography coupled with mass spectrometric detection (LC-MS) has an intrinsic problem because most LC peaks elute too fast to perform all possible MS experiments in one single run. To gain more information on-the-fly, chromatographic separation may be slowed down during peak elution however on cost of analysis time. Another simple solution is to perform fraction collection into a 96-well plate or onto a MALDI plate via a post-column split during LC-MS/MS analyses. This setup is particularly interesting because it allows to archive the LC-MS analysis. Furthermore, automated nanoelectrospray chip-based infusion or matrix-assisted laser desorption ionization (MADLI) is particularly attractive to rapidly re-analyze the fraction of interest independent of the LC run. The decoupling of chromatography from mass spectrometric detection brings also the benefit that it allows to multiplex analyses and therefore improve analytical throughput. For all these approaches, downscaling of the chromatographic separations is of great interest.

MALDI combined with time-of-flight mass spectrometry is largely used for the analysis of peptides and proteins however its potential for the ionization of low molecular weight compounds as also been demonstrated. The present work used an experimental MALDI source mounted onto a triple quadrupole linear ion trap and investigated the potential of MALDI for structural elucidation of metabolites. Because time is not anymore an issue the selective scan mode such as neutral loss or precursor ion scan be used more efficiently. Once the precursor ions candidates have been identified sensitive product ion and MS3 spectra can be recorded. The approach will be presented is details as well as its application for the identification of metabolites from several compounds of pharmaceutical interest.