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

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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.

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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.

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Authors and Affiliations

  1. W.M. Keck Fourier Transform Mass Spectrometry Laboratory, Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA

    Mark T. Bokhart, Elias Rosen & David C. Muddiman

  2. Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Corbin Thompson, Craig Sykes & Angela D. M. Kashuba

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  1. Mark T. Bokhart
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  2. Elias Rosen
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  3. Corbin Thompson
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  4. Craig Sykes
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  5. Angela D. M. Kashuba
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  6. David C. Muddiman
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Correspondence to David C. Muddiman.

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Published in the topical collection Mass Spectrometry Imaging with guest editors Andreas Römpp and Uwe Karst.

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Bokhart, M.T., Rosen, E., Thompson, C. et al. Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization. Anal Bioanal Chem 407, 2073–2084 (2015). https://doi.org/10.1007/s00216-014-8220-y

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