Matrix-Assisted Laser Desorption Ionization Imaging Mass Spectrometry of Drug Distribution in Mouse Brain Tissue by High-Resolution Time-of-Flight Mass Spectrometry

  • Takaya SatohEmail author
  • Ayumi Kubo
  • Hisanao Hazama
Part of the Methods in Molecular Biology book series (MIMB, volume 1810)


Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry provides the opportunity to visualize the distributions of drugs and metabolites in tissue specimens without requiring radioisotopes, as are used for whole-body autoradiography. However, the analysis of low-molecular-weight compounds is often difficult using the common reflectron-type MALDI time-of-flight mass spectrometers. Insufficient mass resolving power causes overlapping of the target drug peak with matrix compound or surface contaminant peaks. To solve this issue, we describe the procedure for imaging mass spectrometry using a high-mass-resolution mass spectrometer that can separate isobaric peaks.

Key words

Imaging mass spectrometry High mass-resolution Drug analysis Accurate mass analysis MS/MS analysis 


  1. 1.
    Smith J, Jones M Jr, Houghton L et al (1999) Future of health insurance. N Engl J Med 965:325–329Google Scholar
  2. 2.
    Valeriani G, Corazza O, Bersani FS et al (2015) Olanzapine as an ideal “trip terminator”? Analysis of online reports relating to antipsychotics’ use and misuse following occurrence of novel psychoactive substance-related psychotic symptoms. Hum Psychopharmacol Clin Exp 30:249–254CrossRefGoogle Scholar
  3. 3.
    Reeves RR (2007) Abuse of olanzapine by substance abusers. J Psychoactive Drugs 39:297–299CrossRefPubMedGoogle Scholar
  4. 4.
    Jungmann JH, Heeren RM (2012) Emerging technologies in mass spectrometry imaging. J Proteome 75(16):5077–5092CrossRefGoogle Scholar
  5. 5.
    Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69:4751–4760CrossRefPubMedGoogle Scholar
  6. 6.
    Rubakhin SS, Jurchen JC, Monroe EB, Sweedler JV (2005) Imaging mass spectrometry: fundamentals and applications to drug discovery. Drug Discov Today 10:823–837CrossRefPubMedGoogle Scholar
  7. 7.
    Solon EG, Schweitzer A, Stoeckli M, Prideaux B (2010) Autoradiography, MALDI-MS, and SIMS-MS imaging in pharmaceutical discovery and development. AAPS J 12(1):11–26CrossRefPubMedGoogle Scholar
  8. 8.
    Greer T, Sturm R, Li L (2011) Mass spectrometry imaging for drugs and metabolites. J Proteome 74:2617–2631CrossRefGoogle Scholar
  9. 9.
    Ait-Belkacem R, Sellami L, Villard C, DePauw E, Calligaris D, Lafitte D (2012) Mass spectrometry imaging is moving toward drug protein co-localization. Trends Biotechnol 3(9):466–474CrossRefGoogle Scholar
  10. 10.
    Lietz CB, Gemperline E, Li L (2013) Qualitative and quantitative mass spectrometry imaging of drugs and metabolites. Adv Drug Deliv Rev 65:1074–1085CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bodzon-Kulakowska A, Suder P (2016) Imaging mass spectrometry: instrumentation, applications, and combination with other visualization techniques. Mass Spectrom Rev 35:147–169CrossRefPubMedGoogle Scholar
  12. 12.
    Satoh T, Sato T, Tamura J (2007) Development of a high-performance MALDI-TOF mass spectrometer utilizing a spiral ion trajectory. J Am Soc Mass Spectrom 18:1318–1323CrossRefPubMedGoogle Scholar
  13. 13.
    Satoh T, Kubo A, Hazama H, Awazu K, Toyoda M (2014) Separation of isobaric compounds using a spiral orbit type time-of-flight mass spectrometer, MALDI-SpiralTOF. Mass Spectrom 3:S0027CrossRefGoogle Scholar
  14. 14.
    Satoh T, Sato T, Kubo A, Tamura J (2011) Tandem time-of-flight mass spectrometer with high precursor ion selectivity employing spiral ion trajectory and improved offset parabolic reflectron. J Am Soc Mass Spectrom 22:797–803CrossRefPubMedGoogle Scholar
  15. 15.
    Satoh T, Kubo A, Shimma S, Toyoda M (2012) Mass spectrometry imaging and structural analysis of lipids directly on tissue specimens by using a spiral orbit type tandem time-of-flight mass spectrometer, spiral TOF-TOF. Mass Spectrom 1:A0013CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.JEOL Ltd.TokyoJapan
  2. 2.Osaka UniversityOsakaJapan

Personalised recommendations