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

Autor: Neilly, J, Gagne, G, Vogt, A, Fagerland, J, Miesbauer, L, Burton, R, Shen, J
Zdroj: Microscopy and Microanalysis; August 2001, Vol. 7 Issue: 1, Number 1 Supplement 2 p632-633, 2p
Abstrakt: 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).
Databáze: Supplemental Index