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Analysis for Parent Drug and Drug Metabolite in Rat Liver, Bile Stones, and Bile Using Microscopy, Laser Capture Microdissection and Analytical Chemistry Techniques

Published online by Cambridge University Press:  02 July 2020

J. Neilly ,
G. Gagne ,
A. Vogt ,
J. Fagerland ,
L. Miesbauer ,
R. Burton  and
J. Shen
J. Neilly
Affiliation:
Department of Microscopy and Microanalysis, Abbott Laboratories, Abbott Park, IL, 60064
G. Gagne
Affiliation:
Department of Microscopy and Microanalysis, Abbott Laboratories, Abbott Park, IL, 60064
A. Vogt
Affiliation:
Department of Microscopy and Microanalysis, Abbott Laboratories, Abbott Park, IL, 60064
J. Fagerland
Affiliation:
Department of Microscopy and Microanalysis, Abbott Laboratories, Abbott Park, IL, 60064
L. Miesbauer
Affiliation:
Department of Structural Chemistry, Abbott Laboratories, Abbott Park, IL , 60064
R. Burton
Affiliation:
Department of Structural Chemistry, Abbott Laboratories, Abbott Park, IL , 60064
J. Shen
Affiliation:
Department of Structural Chemistry, Abbott Laboratories, Abbott Park, IL , 60064
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Abstract

Microscopy, microdissection, and analytical chemistry techniques were used to localize and identify drug and drug metabolites in specimens from drug-treated rats. During a toxicology study in rats of a drug candidate, concretions (stones) were found in the common bile duct, and pigmented material was found in hepatocytes and liver macrophages after long-term exposure to the drug. Because a recent study showed the effective use of microscopy and mass spectrometry (MS) to identify drug metabolite in tissue sections, we used similar methods to confirm that pigmented material in liver cells was drug metabolite. Energy dispersive x-ray spectroscopy (EDS) suggested that drug and/or metabolite were also present in stones.

Pigmented hepatocytes and macrophages in frozen sections of unfixed liver exhibited fluorescence similar to that of parent drug. When excited by UV illumination, these cells fluoresced the same color blue as the bulk drug (Fig. 1).

Type
Microscopy, Microanalysis and Imaging in the Pharmaceutical Industry (Organized by S. Samuelsson and B. Maleeff)
Information
Microscopy and Microanalysis , Volume 7 , Issue S2: Proceedings: Microscopy & Microanalysis 2001, Microscopy Society of America 59th Annual Meeting, Microbeam Analysis Society 35th Annual Meeting, Long Beach, California August 5-9, 2001 , August 2001 , pp. 632 - 633
Copyright
Copyright © Microscopy Society of America 2001

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References

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