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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]
+ Show Author Affiliations
  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 Laboratory (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:
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.
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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. https://doi.org/10.1016/j.chroma.2015.10.093
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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. https://doi.org/10.1016/j.chroma.2015.10.093. https://www.osti.gov/servlets/purl/1241465.
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@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},
number = C,
volume = 1439,
place = {United States},
year = {Tue Nov 03 00:00:00 EST 2015},
month = {Tue Nov 03 00:00:00 EST 2015}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1016/j.chroma.2015.10.093
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Works referenced in this record:

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An enhanced droplet-based liquid microjunction surface sampling system coupled with HPLC-ESI-MS/MS for spatially resolved analysis
journal, November 2014

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Ambient DESI and LESA-MS Analysis of Proteins Adsorbed to a Biomaterial Surface Using In-Situ Surface Tryptic Digestion
journal, September 2013

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Sensitive determination of a drug candidate in dried blood spots using a TLC–MS interface integrated into a column-switching LC–MS/MS system
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Clinical Pharmacokinetics and Pharmacodynamics of Repaglinide
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    Works referencing / citing this record:

    Quantitative Imaging of Proteins in Tissue by Stable Isotope Labeled Mimetic Liquid Extraction Surface Analysis Mass Spectrometry
    journal, October 2019

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