A quantitation method for mass spectrometry imaging.

A new quantitation method for mass spectrometry imaging (MSI) with matrix-assisted laser desorption/ionization (MALDI) has been developed. In this method, drug concentrations were determined by tissue homogenization of five 10 µm tissue sections adjacent to those analyzed by MSI. Drug levels in tissue extracts were measured by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The integrated MSI response was correlated to the LC/MS/MS drug concentrations to determine the amount of drug detected per MSI ion count. The study reported here evaluates olanzapine in liver tissue. Tissue samples containing a range of concentrations were created from liver harvested from rats administered a single dose of olanzapine at 0, 1, 4, 8, 16, 30, or 100 mg/kg. The liver samples were then analyzed by MALDI-MSI and LC/MS/MS. The MALDI-MSI and LC/MS/MS correlation was determined for tissue concentrations of ~300 to 60,000 ng/g and yielded a linear relationship over two orders of magnitude (R(2) = 0.9792). From this correlation, a conversion factor of 6.3 ± 0.23 fg/ion count was used to quantitate MSI responses at the pixel level (100 µm). The details of the method, its importance in pharmaceutical analysis, and the considerations necessary when implementing it are presented.

[1]  A. Pitt,et al.  Mass spectrometry imaging of pharmacological compounds in tissue sections. , 2010, Bioanalysis.

[2]  M. Clench,et al.  Examination of the distribution of the bioreductive drug AQ4N and its active metabolite AQ4 in solid tumours by imaging matrix-assisted laser desorption/ionisation mass spectrometry. , 2007, Rapid communications in mass spectrometry : RCM.

[3]  M. Karas,et al.  Matrix-assisted ultraviolet laser desorption of non-volatile compounds , 1987 .

[4]  Alain Schweitzer,et al.  Autoradiography, MALDI-MS, and SIMS-MS Imaging in Pharmaceutical Discovery and Development , 2010, The AAPS Journal.

[5]  G. V. Van Berkel,et al.  Fully automated liquid extraction-based surface sampling and ionization using a chip-based robotic nanoelectrospray platform. , 2010, Journal of mass spectrometry : JMS.

[6]  Jonathan V Sweedler,et al.  Vitamin E imaging and localization in the neuronal membrane. , 2005, Journal of the American Chemical Society.

[7]  Walter A. Korfmacher,et al.  Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissue. , 2006, Rapid communications in mass spectrometry : RCM.

[8]  A. Brunet,et al.  Complementary advantages of fluorescence and SIMS microscopies in the study of cellular localization of two new antitumor drugs , 1997, Microscopy research and technique.

[9]  R. Caprioli,et al.  Imaging mass spectrometry: Towards clinical diagnostics , 2008, Proteomics. Clinical applications.

[10]  S. Chandra,et al.  SIMS ion microscopy imaging of boronophenylalanine (BPA) and 13C15N-labeled phenylalanine in human glioblastoma cells: Relevance of subcellular scale observations to BPA-mediated boron neutron capture therapy of cancer , 2007 .

[11]  Alexander K. Mullen,et al.  Determination of agrochemical compounds in soya plants by imaging matrix-assisted laser desorption/ionisation mass spectrometry. , 2005, Rapid communications in mass spectrometry : RCM.

[12]  Thomas E. Fehniger,et al.  Fine Mapping the Spatial Distribution and Concentration of Unlabeled Drugs within Tissue Micro-Compartments Using Imaging Mass Spectrometry , 2010, PloS one.

[13]  Walter A. Korfmacher,et al.  Visualization of first-pass drug metabolism of terfenadine by MALDI-imaging mass spectrometry. , 2008, Drug Metabolism Letters.

[14]  M. Setou,et al.  Thin Sectioning Improves the Peak Intensity and Signal-to-Noise Ratio in Direct Tissue Mass Spectrometry , 2006 .

[15]  Walter A. Korfmacher,et al.  Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry. , 2003, Journal of mass spectrometry : JMS.

[16]  Lisa H Cazares,et al.  Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue , 2009, Clinical Cancer Research.

[17]  A. Woods,et al.  Brain tissue lipidomics: Direct probing using matrix-assisted laser desorption/ionization mass spectrometry , 2006, The AAPS Journal.

[18]  Richard M. Caprioli,et al.  MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. , 2008, Analytical chemistry.

[19]  A. Pitt,et al.  Use of a solvent-free dry matrix coating for quantitative matrix-assisted laser desorption ionization imaging of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate in rat brain and quantitative analysis of the drug from laser microdissected tissue regions. , 2010, Analytical chemistry.

[20]  R. Caprioli,et al.  Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. , 2006, Analytical chemistry.

[21]  N. Palomero-Gallagher,et al.  Imaging of copper, zinc, and other elements in thin section of human brain samples (hippocampus) by laser ablation inductively coupled plasma mass spectrometry. , 2005, Analytical chemistry.

[22]  A. Ewing,et al.  Secondary ion MS imaging to relatively quantify cholesterol in the membranes of individual cells from differentially treated populations. , 2007, Analytical chemistry.

[23]  T. Covey,et al.  Characterization and performance of MALDI on a triple quadrupole mass spectrometer for analysis and quantification of small molecules. , 2005, Analytical chemistry.

[24]  A. Vertes,et al.  Atmospheric pressure infrared MALDI imaging mass spectrometry for plant metabolomics. , 2008, Analytical chemistry.

[25]  R. Cooks,et al.  Ambient Mass Spectrometry , 2006, Science.

[26]  Douglas Benson,et al.  High-resolution quantitative imaging of mammalian and bacterial cells using stable isotope mass spectrometry , 2006, Journal of biology.

[27]  Tyler A. Zimmerman,et al.  Chapter 13: Imaging of cells and tissues with mass spectrometry: adding chemical information to imaging. , 2008, Methods in cell biology.

[28]  Richard M Caprioli,et al.  Automated acoustic matrix deposition for MALDI sample preparation. , 2006, Analytical chemistry.

[29]  W. Niederberger,et al.  A simple method for the quantitation of 14C-whole-body autoradiograms. , 1987, International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes.

[30]  V. Dressler,et al.  Imaging of metals and metal-containing species in biological tissues and on gels by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS): A new analytical strategy for applications in life sciences , 2008 .

[31]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[32]  Edward S Yeung,et al.  High-spatial and high-mass resolution imaging of surface metabolites of Arabidopsis thaliana by laser desorption-ionization mass spectrometry using colloidal silver. , 2010, Analytical chemistry.

[33]  J. Sweedler,et al.  Spatial correlation of confocal Raman scattering and secondary ion mass spectrometric molecular images of lignocellulosic materials. , 2010, Analytical chemistry.

[34]  M. Stoeckli,et al.  Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues , 2001, Nature Medicine.

[35]  M. Clench,et al.  Matrix-assisted laser desorption/ionization-ion mobility separation-mass spectrometry imaging of vinblastine in whole body tissue sections. , 2008, Analytical chemistry.

[36]  R. Caprioli,et al.  Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. , 1997, Analytical chemistry.

[37]  L. Signor,et al.  Analysis of erlotinib and its metabolites in rat tissue sections by MALDI quadrupole time-of-flight mass spectrometry. , 2007, Journal of mass spectrometry : JMS.

[38]  A. Woods,et al.  Localization and analyses of small drug molecules in rat brain tissue sections. , 2005, Analytical chemistry.

[39]  O. Ovchinnikova,et al.  Established and emerging atmospheric pressure surface sampling/ionization techniques for mass spectrometry. , 2008, Journal of mass spectrometry : JMS.

[40]  D. C. Perdian,et al.  Imaging MS methodology for more chemical information in less data acquisition time utilizing a hybrid linear ion trap-orbitrap mass spectrometer. , 2010, Analytical chemistry.

[41]  M. Ohmura,et al.  Paradoxical ATP elevation in ischemic penumbra revealed by quantitative imaging mass spectrometry. , 2010, Antioxidants & redox signaling.

[42]  E. Voigtman,et al.  Reduction of electronic noise in inductively coupled plasma atomic emission and fluorescence spectrometric measurements , 1983 .

[43]  S. Marder,et al.  Pharmacokinetics and tissue distribution of olanzapine in rats , 1999, Biopharmaceutics & drug disposition.

[44]  R. Oballa,et al.  Comparison of MALDI to ESI on a triple quadrupole platform for pharmacokinetic analyses. , 2007, Analytical chemistry.

[45]  S. Chandra.  Quantitative imaging of chemical composition in single cells by secondary ion mass spectrometry: cisplatin affects calcium stores in renal epithelial cells. , 2010, Methods in molecular biology.