title: A mass spectrometry based imaging method developed for the intracellular detection of HIV protease inhibitors.
abstract: Mass spectrometry imaging is a promising technique for measuring drugs and drug metabolites in cells and tissues. In this manuscript we describe a method for the imaging of HIV protease inhibitors. As a model system we used Mono Mac 6 cells cultured with the HIV protease inhibitors saquinavir and nelfinavir deposited on glass slides using a cytocentrifuge. A sublimation/deposition device for homogeneous matrix deposition was constructed which allows imaging of these HIV protease inhibitors at clinically relevant concentrations. Using this matrix sublimation/deposition method, glass slides containing the cytocentrifuged cells can be measured and analyzed by two types of mass spectrometry techniques, viz. matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and MALDI Fourier transform ion cyclotron resonance (FTICR), and this makes it possible to perform imaging rapidly (MALDI-TOF) and with a very high selectivity (MALDI-FTICR).
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, The Netherlands. l.dekker@erasmusmc.nl
authors.forename: Lennard J M
authors.initials: LJ
authors.lastname: Dekker
authors.forename: Jeroen J A
authors.initials: JJ
authors.lastname: van Kampen
authors.forename: Mariska L
authors.initials: ML
authors.lastname: Reedijk
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burgers
authors.forename: Rob A
authors.initials: RA
authors.lastname: Gruters
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
mesh_terms: D002460:Cell Line; D017357:Cyclotrons; D004867:Equipment Design; D017320:HIV Protease Inhibitors / Q000032:analysis*; D007089:Image Enhancement / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D019888:Nelfinavir / Q000032:analysis; D019258:Saquinavir / Q000032:analysis; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013997:Time Factors
chemical_list: D017320:HIV Protease Inhibitors; D019888:Nelfinavir; D019258:Saquinavir