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

Weiqi Chen, Lifei Wang, Gary J. Van Berkel, Vilmos Kertesz, Jinping Gan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 were studied. Major organs (brain, lung, liver, kidney and 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. In addition, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.

Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalJournal of Chromatography A
Volume1439
DOIs
StatePublished - Mar 25 2016

Funding

W.C., L.W. and J.G. would like to thank Mr. Markus Fancher and the Technical Support Unit at Bristol-Myers Squibb for assistance in animal handling and dosing. Support for V.K. and G.J.V.B. was provided through a Cooperative Research and Development Agreement with Sciex (CRADA NFE-10-02966). The software package LMJ Points Plus © V2.98 was previously developed with support from the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division.

Keywords

  • Autosampler
  • Droplet-based liquid extraction
  • Liquid microjunction
  • Quantitation
  • Repaglinide
  • Spatial distribution

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