Abstract
A technique for rapidly screening drugs and other compounds for possible glucuronide formation has been developed. The drug is either added to the perfusate of an isolated perfused rat liver or injected directly into the portal vein of an anesthetized rat. Bile is collected, dried, and permethylated with dimethyl sulfoxide sodium salt and methyl iodide. The product mixture is analyzed by mass spectrometry through both the direct and gas chromatography inlets. Glucuronides are identified by the presence of major ions at m/e 101 and m/e 201. Intact glucuronides of hydroxydiphenylhydantoin, hydroxymephobarbital (or hydroxyphenobarbital), hydroxyhexobarbital, chloramphenicol, 2-methyl-1,4-dihydroxynaphthalene (reduced menadione), and others have been detected. The technique can be conveniently applied to 1-5 µl of bile (estimated 0.1-1 µg of drug or each metabolite). Other metabolites can also be identified.
Footnotes
- Received November 6, 1972.
- Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics
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