Microbial models of mammalian metabolism. N-dealkylation of furosemide to yield the mammalian metabolite CSA using Cunninghamella elegans.

M Hezari, P J Davis

Index: Drug Metab. Dispos. 20(6) , 882-8, (1992)

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Abstract

Furosemide (Lasix), a widely used diuretic, is metabolized by the fungus Cunninghamella elegans (ATCC 36112) to 4-chloro-5-sulfamoyl anthranilic acid (CSA), a metabolite also present in mammalian systems. This metabolite was isolated following preparative-scale incubations of C. elegans, and was characterized by comparison with standard CSA using 13C-NMR, mass spectrometry (high-resolution mass spectra, electron impact mass spectra), UV, TLC, and HPLC with fluorescence detection. Because a known complication with furosemide studies is the spontaneous formation of CSA by decomposition of furosemide during incubation, extraction, and/or analysis, a time course study was conducted to determine the rate of CSA formation caused by metabolism vs. the relatively low rate of CSA formation caused by spontaneous decomposition.