Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C)

H. Frederiksen, Henrik Lauritz Frandsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAalphaC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeAalphaC in rats was investigated. Rats were dosed with tritium-labeled MeAalphaC, and urine and feces were collected over 3 days. The metabolites of MeAalphaC were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with beta-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeAalphaC was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeAalphaC-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeAalphaC and two phase I metabolites, 6-OH-MeAalphaC and 7-OH-MeAalphaC, the following conjugated metabolites were identified: MeAalphaC-N-2-glucuronide, AalphaC-3-CH2O-glucuronide, 3-carboxy-AalphaC and 3-carboxy-AalphaC-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeAalphaC and 7-OH-MeAalphaC. Also, a large amount of a rather unstable compound proposed to be of MeAalphaC-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeAalphaC and 7-OH-MeAalphaC were the only compounds identified in feces. Any activated metabolites of MeAalphaC were not detected in rat urine or feces.
Original languageEnglish
JournalDrug Metabolism and Disposition
Volume32
Issue number6
Pages (from-to)661-665
ISSN0090-9556
Publication statusPublished - 2004

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