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Title: Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

Abstract

Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.

Authors:
 [1];  [1];  [2];  [1];  [2]
  1. Bristol-Myers Squibb Pharmaceutical Research & Development, Princeton, NJ (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1241465
Alternate Identifier(s):
OSTI ID: 1252496
Grant/Contract Number:  
AC05-00OR22725; NFE-10-02966
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Chromatography
Additional Journal Information:
Journal Volume: 1439; Journal Issue: C; Journal ID: ISSN 0021-9673
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; liquid microjunction; droplet-based liquid extraction; quantitation; autosampler; spatial distribution; repaglinide

Citation Formats

Chen, Weiqi, Wang, Lifei, Van Berkel, Gary J., Gan, Jinping, and Kertesz, Vilmos. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. United States: N. p., 2015. Web. doi:10.1016/j.chroma.2015.10.093.
Chen, Weiqi, Wang, Lifei, Van Berkel, Gary J., Gan, Jinping, & Kertesz, Vilmos. Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. United States. doi:10.1016/j.chroma.2015.10.093.
Chen, Weiqi, Wang, Lifei, Van Berkel, Gary J., Gan, Jinping, and Kertesz, Vilmos. Tue . "Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry". United States. doi:10.1016/j.chroma.2015.10.093. https://www.osti.gov/servlets/purl/1241465.
@article{osti_1241465,
title = {Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry},
author = {Chen, Weiqi and Wang, Lifei and Van Berkel, Gary J. and Gan, Jinping and Kertesz, Vilmos},
abstractNote = {Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites was studied. Major organs (brain, lung, liver, kidney, muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. Furthermore, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.},
doi = {10.1016/j.chroma.2015.10.093},
journal = {Journal of Chromatography},
issn = {0021-9673},
number = C,
volume = 1439,
place = {United States},
year = {2015},
month = {11}
}

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