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

Journal Article · Wed Jan 10 00:00:00 EST 2018 · International Journal of Mass Spectrometry

DOI:https://doi.org/10.1016/j.ijms.2018.01.005· OSTI ID:1493155

Kertesz, Vilmos ^[1]; Vavrek, Marissa ^[2]; Freddo, Carol ^[2]; Van Berkel, Gary J. ^[1]

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1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
2. Merck Research Labs, West Point, PA (United States)

Here, 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-μm-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.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
• Grant/Contract Number: AC05-00OR22725
• OSTI ID: 1493155
• Journal Information: International Journal of Mass Spectrometry, Journal Name: International Journal of Mass Spectrometry Journal Issue: C Vol. 437; ISSN 1387-3806
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ATSP-7041
Autosampler
Droplet-based liquid extraction
Liquid microjunction
Spatial distribution
Stapled peptide
Surface sampling