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J Chromatogr B Biomed Sci Appl. 2000 May 12;741(2):205-11.

Identification of the principal circulating metabolite of a synthetic 5,4'-diaminoflavone (NSC 686288), an antitumor agent, in the rat.

Author information

1
Laboratory of Drug Discovery, Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, MD 21701, USA. 1p5q@nih.gov

Abstract

During the course of our study to develop analytical methodology for quantitating the investigative antitumor agent 5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran -4-one (DAF; NSC 686288) in plasma, a significant concentration of a metabolite was observed in a post-dosed rat. The results of electron-ionization (EI) mass spectrometric analysis of the metabolite suggested that N-acetylation had occurred, but, interestingly, that only one of the compound's two primary amino groups had been transformed. Comparing the mass spectra and gas chromatographic retention times of a mono-acetylated sample of DAF and that of the metabolite showed both to be the same. A retro-Diels-Alder (RDA) fragmentation of the B ring of DAF results in formation of two abundant product ions, each retaining one of the amino groups. The EI mass spectrum of mono-N-acetamido-d3 DAF shows loss of ketene-d2, leading to formation of an -NHD group. The ensuing RDA fragmentation easily identifies which of the two product ions contains the deuterium, thereby allowing us to assign the site of N-acetylation as the amino group on ring C (the 4' position) of DAF.

PMID:
10872590
DOI:
10.1016/s0378-4347(00)00094-3
[Indexed for MEDLINE]

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