Novel mass spectrometry imaging software assisting labeled normalization and quantitation of drugs and neuropeptides directly in tissue sections

J Proteomics. 2012 Aug 30;75(16):4941-4951. doi: 10.1016/j.jprot.2012.07.034. Epub 2012 Jul 27.

Abstract

MALDI MS imaging has been extensively used to produce qualitative distribution maps of proteins, peptides, lipids, small molecule pharmaceuticals and their metabolites directly in biological tissue sections. There is growing demand to quantify the amount of target compounds in the tissue sections of different organs. We present a novel MS imaging software including protocol for the quantitation of drugs, and for the first time, an endogenous neuropeptide directly in tissue sections. After selecting regions of interest on the tissue section, data is read and processed by the software using several available methods for baseline corrections, subtractions, denoising, smoothing, recalibration and normalization. The concentrations of in vivo administered drugs or endogenous compounds are then determined semi-automatically using either external standard curves, or by using labeled compounds, i.e., isotope labeled analogs as standards. As model systems, we have quantified the distribution of imipramine and tiotropium in the brain and lung of dosed rats. Substance P was quantified in different mouse brain structures, which correlated well with previously reported peptide levels. Our approach facilitates quantitative data processing and labeled standards provide better reproducibility and may be considered as an efficient tool to quantify drugs and endogenous compounds in tissue regions of interest.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Diagnostic Imaging / instrumentation
  • Diagnostic Imaging / methods
  • Electronic Data Processing / instrumentation
  • Electronic Data Processing / methods
  • Male
  • Mass Spectrometry / instrumentation*
  • Mass Spectrometry / methods*
  • Mice
  • Mice, Inbred C57BL
  • Microtomy
  • Neuropeptides / analysis*
  • Neuropeptides / metabolism
  • Pharmaceutical Preparations / analysis*
  • Pharmaceutical Preparations / metabolism
  • Rats
  • Rats, Wistar
  • Reference Standards
  • Software*
  • Specimen Handling
  • Staining and Labeling / instrumentation
  • Staining and Labeling / standards*
  • Tissue Distribution

Substances

  • Neuropeptides
  • Pharmaceutical Preparations