期刊
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
卷 407, 期 8, 页码 2073-2084出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00216-014-8220-y
关键词
Mass spectrometry imaging; IR-MALDESI; Absolute quantification; Drug distribution; HIV; Selected reaction monitoring
资金
- National Institutes of Health [R01GM087964]
- W.M. Keck Foundation
- North Carolina State University
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI096113, R01AI111891, P30AI050410] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM087964] Funding Source: NIH RePORTER
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 mu g/g(tissue). 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 mu g/g(tissue).
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