Journal Article

Identification of urine metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-<i>b</i>]pyridine following consumption of a single cooked chicken meal in humans

Kristen S. Kulp, Mark G. Knize, Michael A. Malfatti, Cynthia P. Salmon and James S. Felton

in Carcinogenesis

Volume 21, issue 11, pages 2065-2072
Published in print November 2000 | ISSN: 0143-3334
Published online November 2000 | e-ISSN: 1460-2180 | DOI:
Identification of urine metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine following consumption of a single cooked chicken meal in humans

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics


Show Summary Details


Many studies suggest that mutagenic/carcinogenic chemicals in the diet, like 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), may play a role in human cancer initiation. We have developed a method to quantify PhIP metabolites in human urine and have applied it to samples from female volunteers who had eaten a meal of cooked chicken. For this analysis, urine samples (5 ml) were spiked with a deuterium-labeled internal standard, adsorbed to a macroporous polymeric column and then eluted with methanol. After a solvent exchange to 0.01 M HCl, the urine extracts were passed through a filter, applied to a benzenesulfonic acid column, washed with methanol/acid and eluted with ammonium acetate and concentrated on a C18 column. The metabolites were eluted from the C18 column and quantified by LC/MS/MS. In our studies of human PhIP metabolism, eight volunteers were fed 200 g of cooked chicken containing a total of 27 μg PhIP. Urine samples were collected for 24 h after the meal, in 6 h aliquots. Although no metabolites could be found in urine collected from volunteers before eating the chicken, four major human PhIP metabolites, N2-OH-PhIP-N2-glucuronide, PhIP-N2-glucuronide, 4'-PhIP-sulfate and N2-OH-PhIP-N3-glucuronide, were found in the urine after the chicken meal. The volunteers in the study excreted 4–53% of the ingested PhIP dose in the urine. The rate of metabolite excretion varied among the subjects, however, in all of the subjects the majority of the metabolites were excreted in the first 12 h. Very little metabolite was detected in the urine after 18 h. In humans, N2-OH-PhIP-N2 glucuronide is the most abundant urinary metabolite, followed by PhIP-N2-glucuronide. The variation seen in the total amount, excretion time and metabolite ratios with our method suggests that individual digestion, metabolism and/or other components of the diet may influence the absorption and amounts of metabolic products produced from PhIP.

Keywords: 4'-hydroxy-PhIP, 2-amino-1-methyl-6-(4'-hydroxy)phenylimidazo[4,5-b]pyridine; N-hydroxy-PhIP, 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine; PhIP, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine.

Journal Article.  6522 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.