Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM Assay

• Published in: Journal of the American Society for Mass Spectrometry 2014-12, Vol.25 (12), p.2038-2047
• Main Authors: Barry, Jeremy A., Robichaud, Guillaume, Bokhart, Mark T., Thompson, Corbin, Sykes, Craig, Kashuba, Angela D. M., Muddiman, David C.
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - analysis; Adenine - chemistry; Adenine - pharmacokinetics; Analytical Chemistry; Anti-Retroviral Agents - analysis; Anti-Retroviral Agents - chemistry; Anti-Retroviral Agents - pharmacokinetics; Antiretroviral drugs; Bioinformatics; Biotechnology; Cervix Uteri - chemistry; Cervix Uteri - metabolism; Chemistry; Chemistry and Materials Science; Chromatography, Liquid - methods; Deoxycytidine - analogs & derivatives; Deoxycytidine - analysis; Deoxycytidine - chemistry; Deoxycytidine - pharmacokinetics; Emtricitabine; Female; Focus: Advancing High Performance Mass Spectrometry: Research Article; Histocytochemistry; Humans; Imaging; Mass spectrometry; Molecular Imaging - methods; Organic Chemistry; Organophosphonates - analysis; Organophosphonates - chemistry; Organophosphonates - pharmacokinetics; Proteomics; Pyrrolidinones - analysis; Pyrrolidinones - chemistry; Pyrrolidinones - pharmacokinetics; Raltegravir Potassium; Selectivity; Spatial distribution; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Tandem Mass Spectrometry - methods; Tenofovir; Tissue Distribution
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1007/s13361-014-0884-1

This work describes the coupling of the IR-MALDESI imaging source with the Q Exactive mass spectrometer. IR-MALDESI MSI was used to elucidate the spatial distribution of several HIV drugs in cervical tissues that had been incubated in either a low or high concentration. Serial sections of those analyzed by IR-MALDESI MSI were homogenized and analyzed by LC-MS/MS to quantify the amount of each drug present in the tissue. By comparing the two techniques, an agreement between the average intensities from the imaging experiment and the absolute quantities for each drug was observed. This correlation between these two techniques serves as a prerequisite to quantitative IR-MALDESI MSI. In addition, a targeted MS 2 imaging experiment was also conducted to demonstrate the capabilities of the Q Exactive and to highlight the added selectivity that can be obtained with SRM or MRM imaging experiments. Fig. a ᅟ