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Spatial Profiling of Stapled α–helical Peptide Atsp-7041 In Mouse Whole-body Thin Tissue Sections Using Droplet-based Liquid Microjunction Surface Sampling-hplc-esi–ms/ms

by Vilmos Kertesz, Marissa Vavrek, Carol Freddo, Gary J Van Berkel
Publication Type
Journal
Journal Name
International Journal of Mass Spectrometry
Publication Date
Page Numbers
17 to 22
Volume
437

The application of a fully automated autosampler/HPLC-ESI-MS/MS system for spatially resolved quantitative droplet-based liquid extraction surface sampling/profiling of stapled α−helical peptide ATSP-7041 in mouse whole-body thin tissue sections is reported. 20-m-thick serial tissue sections of an ATSP-7041 dosed mouse were prepared and the absolute concentration of the targeted peptide was first determined in different organs using 2.3-mm diameter tissue punches, standard bulk tissue extraction protocols, and subsequent HPLC separation and tandem mass spectrometric analysis. The same organs/locations were then analyzed in neighboring tissue sections using the droplet-based surface sampling approach. The observed ATSP-7041 concentration using this method was always significantly lower than that measured by the tissue punch workflow at the same tissue location of a serial section. Calculated extraction efficiencies were 10.7±0.5% (brain), 11.0±3.2% (liver spot 1), 10.7±2.6% (liver spot 2), 15.0±0.6% (lung) and 12.9±0.7% (blood). While these extraction efficiency values were low, they were reproducible within a given organ. This suggests that once the extraction efficiency is established for a given tissue type and drug, the reproducibility of the droplet-based approach could provide a non-labor intensive and high-throughput means to acquire spatially resolved quantitative analysis of multiple samples of the same type.