Spatial profiling of stapled ??helical peptide ATSP-7041 in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-HPLC-ESI?MS/MS [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 612.3 Digestion

Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018

Mô tả vật lý: Size: p. 17-22 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 261920

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 ??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.
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