title: Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization.
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.
authors.affiliation: W.M. Keck Fourier Transform Mass Spectrometry Laboratory, Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bokhart
authors.forename: Elias
authors.initials: E
authors.lastname: Rosen
authors.forename: Corbin
authors.initials: C
authors.lastname: Thompson
authors.forename: Craig
authors.initials: C
authors.lastname: Sykes
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
authors.forename: David C
authors.initials: DC
authors.lastname: Muddiman
mesh_terms: D003952:Diagnostic Imaging / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006801:Humans; D053918:Papillomavirus Vaccines / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000295:instrumentation / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000175:diagnosis*
chemical_list: D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18