Fulltext

Quantification in MALDI-MS imaging: what can we learn from MALDI-selected reaction monitoring and what can we expect for imaging?

Porta, Tiffany ; Lesur, Antoine ; Varesio, Emmanuel ; Hopfgartner, Gérard

In: Analytical and Bioanalytical Chemistry, 2015, vol. 407, no. 8, p. 2177-2187

Ajouter à la liste personnelle
    Titre
    • Quantification in MALDI-MS imaging: what can we learn from MALDI-selected reaction monitoring and what can we expect for imaging?
    Auteur
    • Porta, Tiffany. Life Sciences Mass Spectrometry, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211, Geneva 4, Switzerland
    • Lesur, Antoine. Life Sciences Mass Spectrometry, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211, Geneva 4, Switzerland
    • Varesio, Emmanuel. Life Sciences Mass Spectrometry, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211, Geneva 4, Switzerland
    • Hopfgartner, Gérard. Life Sciences Mass Spectrometry, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211, Geneva 4, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Analytical and Bioanalytical Chemistry, 2015, vol. 407, no. 8, p. 2177-2187. Springer Berlin Heidelberg
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:332438
    Summary
    Quantification by mass spectrometry imaging (Q-MSI) is one of the hottest topics of the current discussions among the experts of the MS imaging community. If MSI is established as a powerful qualitative tool in drug and biomarker discovery, its reliability for absolute and accurate quantification (QUAN) is still controversial. Indeed, Q-MSI has to deal with several fundamental aspects that are difficult to control, and to account for absolute quantification. The first objective of this manuscript is to review the state-of-the-art ofQ-MSI and the current strategies developed for absolute quantification by direct surface sampling from tissue sections. This includes comments on the quest for the perfect matrix-matched standards and signal normalization approaches. Furthermore, this work investigates quantification at a pixel level to determine how many pixels must be considered for accurate quantification by ultraviolet matrix-assisted laser desorption/ionization (MALDI), the most widely used technique for MSI. Particularly, this study focuses on the MALDI-selected reaction monitoring (SRM) in rastering mode, previously demonstrated as a quantitative and robust approach for small analyte and peptide-targeted analyses. The importance of designing experiments of good quality and the use of a labeled compound for signal normalization is emphasized to minimize the signal variability. This is exemplified by measuring the signal for cocaine and a tryptic peptide (i.e., obtained after digestion of a monoclonal antibody) upon different experimental conditions, such as sample stage velocity, laser power and frequency, or distance between two raster lines. Our findings show that accurate quantification cannot be performed on a single pixel but requires averaging of at least 4-5pixels. The present work demonstrates that MALDI-SRM/MSI is quantitative with precision better than 10-15%, which meets the requirements of most guidelines (i.e., in bioanalysis or toxicology) for quantification of drugs or peptides from tissue homogenates. Graphical Abstract MALDI-SRM/MSI is quantitative with precision better than 10-15 % when instrumental parameters are correctly set and after pixel-by-pixel normalization