Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.

[1]  William McNally,et al.  Quantitative Whole-Body Autoradiographic Determination of Tacrine Tissue Distribution in Rats Following Intravenous or Oral Dose , 2004, Pharmaceutical Research.

[2]  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.

[3]  Josephine Bunch,et al.  Optimisation of colour schemes to accurately display mass spectrometry imaging data based on human colour perception , 2015, Analytical and Bioanalytical Chemistry.

[4]  François Bouzom,et al.  Quantitative mass spectrometry imaging of propranolol and olanzapine using tissue extinction calculation as normalization factor. , 2012, Journal of proteomics.

[5]  Richard A Yost,et al.  Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard. , 2013, Analytical chemistry.

[6]  M. Andersson,et al.  Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization. , 2016, The Analyst.

[7]  Andrew McBride,et al.  Mass spectrometry imaging for dissecting steroid intracrinology within target tissues. , 2013, Analytical chemistry.

[8]  R. Yost,et al.  Identifying tissue-specific signal variation in MALDI mass spectrometric imaging by use of an internal standard. , 2013, Analytical chemistry.

[9]  David C Muddiman,et al.  MSiReader: An Open-Source Interface to View and Analyze High Resolving Power MS Imaging Files on Matlab Platform , 2013, Journal of The American Society for Mass Spectrometry.

[10]  Per E Andrén,et al.  Novel mass spectrometry imaging software assisting labeled normalization and quantitation of drugs and neuropeptides directly in tissue sections. , 2012, Journal of proteomics.

[11]  A. Proctor,et al.  Selection of internal standards for quantitative analysis by matrix-assisted laser desorption-ionization (MALDI) time-of-flight mass spectrometry , 1997 .

[12]  Peter J H Webborn,et al.  Mass spectrometry imaging of cassette-dosed drugs for higher throughput pharmacokinetic and biodistribution analysis. , 2014, Analytical chemistry.

[13]  E. Solon,et al.  Whole-body autoradiography in drug discovery. , 2002, Current drug metabolism.

[14]  P. Edlund,et al.  Determination of corticosteroids in tissue samples by liquid chromatography-tandem mass spectrometry. , 2005, Journal of pharmaceutical and biomedical analysis.

[15]  Brendan Prideaux,et al.  Mass spectrometry imaging for drug distribution studies. , 2012, Journal of proteomics.

[16]  R. Cooks,et al.  Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization , 2004, Science.

[17]  Walter A. Korfmacher,et al.  Liquid extraction surface analysis mass spectrometry (LESA-MS) as a novel profiling tool for drug distribution and metabolism analysis: the terfenadine example. , 2011, Rapid communications in mass spectrometry : RCM.

[18]  P. Chaurand,et al.  Organic ion imaging of biological tissue with secondary ion mass spectrometry and matrix-assisted laser desorption/ionization. , 2001, Journal of mass spectrometry : JMS.

[19]  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.

[20]  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.

[21]  M. Clench,et al.  Determination of pharmaceutical compounds in skin by imaging matrix-assisted laser desorption/ionisation mass spectrometry. , 2004, Rapid communications in mass spectrometry : RCM.

[22]  Harish Shankaran,et al.  Investigating nephrotoxicity of polymyxin derivatives by mapping renal distribution using mass spectrometry imaging. , 2015, Chemical research in toxicology.

[23]  M. Reid Groseclose,et al.  A mimetic tissue model for the quantification of drug distributions by MALDI imaging mass spectrometry. , 2013, Analytical chemistry.

[24]  Peter J H Webborn,et al.  Mapping drug distribution in brain tissue using liquid extraction surface analysis mass spectrometry imaging. , 2015, Analytical chemistry.

[25]  H. Cooper,et al.  Hemoglobin Variant Analysis via Direct Surface Sampling of Dried Blood Spots Coupled with High-Resolution Mass Spectrometry , 2011, Analytical chemistry.

[26]  Nicholas E. Manicke,et al.  Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues , 2008, Proceedings of the National Academy of Sciences.

[27]  R. Cooks,et al.  Tissue imaging at atmospheric pressure using desorption electrospray ionization (DESI) mass spectrometry. , 2006, Angewandte Chemie.