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Analytical and Bioanalytical Chemistry

, Volume 407, Issue 8, pp 2073–2084 | Cite as

Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization

  • Mark T. Bokhart
  • Elias Rosen
  • Corbin Thompson
  • Craig Sykes
  • Angela D. M. Kashuba
  • David C. Muddiman
Research Paper
Part of the following topical collections:
  1. Mass Spectrometry Imaging

Abstract

A quantitative mass spectrometry imaging (QMSI) technique using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is demonstrated for the antiretroviral (ARV) drug emtricitabine in incubated human cervical tissue. Method development of the QMSI technique leads to a gain in sensitivity and removal of interferences for several ARV drugs. Analyte response was significantly improved by a detailed evaluation of several cationization agents. Increased sensitivity and removal of an isobaric interference was demonstrated with sodium chloride in the electrospray solvent. Voxel-to-voxel variability was improved for the MSI experiments by normalizing analyte abundance to a uniformly applied compound with similar characteristics to the drug of interest. Finally, emtricitabine was quantified in tissue with a calibration curve generated from the stable isotope-labeled analog of emtricitabine followed by cross-validation using liquid chromatography tandem mass spectrometry (LC-MS/MS). The quantitative IR-MALDESI analysis proved to be reproducible with an emtricitabine concentration of 17.2 ± 1.8 μg/gtissue. This amount corresponds to the detection of 7 fmol/voxel in the IR-MALDESI QMSI experiment. Adjacent tissue slices were analyzed using LC-MS/MS which resulted in an emtricitabine concentration of 28.4 ± 2.8 μg/gtissue.

Keywords

Mass spectrometry imaging IR-MALDESI Absolute quantification Drug distribution HIV Selected reaction monitoring 

Notes

Acknowledgments

The authors gratefully acknowledge the financial support from the National Institutes of Health (R01GM087964), the W.M. Keck Foundation, and North Carolina State University.

Supplementary material

216_2014_8220_MOESM1_ESM.pdf (509 kb)
ESM 1 (PDF 509 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mark T. Bokhart
    • 1
  • Elias Rosen
    • 1
  • Corbin Thompson
    • 2
  • Craig Sykes
    • 2
  • Angela D. M. Kashuba
    • 2
  • David C. Muddiman
    • 1
  1. 1.W.M. Keck Fourier Transform Mass Spectrometry Laboratory, Department of ChemistryNorth Carolina State UniversityRaleighUSA
  2. 2.Eshelman School of PharmacyThe University of North Carolina at Chapel HillChapel HillUSA

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