ORIGINAL PAPER

Applied Microbiology and Biotechnology

, Volume 53, Issue 3, pp 310-315

Metabolism of the ethanolamine-type antihistamine diphenhydramine (Benadryl)TM by the fungus Cunninghamella elegans

  • J. D. MoodyAffiliated withDivision 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
  • , T. M. HeinzeAffiliated withDivision of Chemistry, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079-9502, USA
  • , E. B. Hansen JrAffiliated withDivision of Chemistry, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079-9502, USA
  • , C. E. CernigliaAffiliated withDivision 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

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.