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

Anal Bioanal Chem. 2015 Mar;407(8):2073-84. doi: 10.1007/s00216-014-8220-y. Epub 2014 Oct 16.


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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diagnostic Imaging / instrumentation
  • Diagnostic Imaging / methods*
  • Female
  • Humans
  • Papillomavirus Vaccines / chemistry*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / instrumentation
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / diagnosis*


  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18