Metabolism of the ethanolamine-type antihistamine diphenhydramine (Benadryl)TM by the fungus Cunninghamella elegans |
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Authors: | J D Moody T M Heinze E B Hansen Jr C E Cerniglia |
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Institution: | (1) Division of Microbiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079-9502, USA e-mail: CCerniglia@nctr.fda.gov Tel.: +1-870-5437341 Fax: +1-870-5437307, US;(2) Division of Chemistry, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079-9502, USA, US |
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Abstract: | Two strains of the filamentous fungus Cunninghamella elegans (ATCC 9245 and ATCC 36112) were grown in Sabouraud dextrose broth and screened for the ability to metabolize the ethanolamine-type
antihistamine diphenhydramine. Based on the amount of parent drug recovered after 7 days incubation, both C. elegans strains metabolized approximately 74% of the diphenhydramine, 58% of this being identified as organic extractable metabolites.
The organic extractable metabolites were isolated by reversed-phase high-performance liquid chromatography and identified
by analyzing their mass and nuclear magnetic resonance spectra. Desorption chemical ionization mass spectrometry (DCIMS) with
deuterated ammonia was used to differentiate possible isobaric diphenhydramine metabolites and to probe the mechanisms of
ion formation under ammonia DCIMS conditions. C. elegans transformed diphenhydramine by demethylation, oxidation, and N-acetylation. The major metabolites observed were diphenhydramine-N-oxide (3%), N-desmethyldiphenhydramine (30%), N-acetyldidesmethyldiphenhydramine (13%), and N-acetyl-N-desmethyldiphenhydramine (12%). These compounds are known mammalian metabolites of diphenhydramine and may be useful for
further toxicological studies.
Received: 24 June 1999 / Revision received: 23 August 1999 / Accepted: 24 September 1999 |
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