title: MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline): metabolism in humans and urinary metabolites in human populations.
abstract: The metabolism of the heterocyclic amines has been extensively studied in rodents and limited studies have been conducted in nonhuman primates. A study has been undertaken on the metabolism of 2-amino-3,8-dimethylimadazo[4,5-f]quinoxaline (MeIQx) in human subjects consuming normal cooked foods. A variety of fish and meat products has been cooked in several ways and fed to human volunteers. Urine was collected and analyzed according to methods developed for this purpose. Earlier rodent studies using radioactive MeIQx had suggested that the principal urinary excretion products included unmetabolized MeIQx, MeIQx sulfamate and MeIQx N-glucuronide. Conditions were developed for HPLC analysis of the free amine and its conjugates in human urine and for total hydrolysis of the conjugates to the free amine. Extraction and cleanup from urine were made possible by the availability of suitable monoclonal antibodies to MeIQx which could be used for immunoaffinity chromatography. For sensitive detection of the amounts present in human urine, gas chromatographymass spectrometry (GC-MS) was used in the negative chemical ionization mode. These studies have demonstrated that the distribution of metabolites in humans strongly resembles that in the rat. The sulfamate and N-glucuronide appear to be predominant human metabolites, while no evidence could be found of N-acetyl MeIQx. Subsequent to the studies just described, the methods developed were applied to urines collected in an epidemiological study on aromatic amine metabolism in Los Angeles. The study includes African American, White, and Asian people who have been phenotyped for caffeine acetylator status.
authors.affiliation: Massachusetts Institute of Technology, Department of Chemistry, Cambridge.
authors.forename: S R
authors.initials: SR
authors.lastname: Tannenbaum
authors.forename: W G
authors.initials: WG
authors.lastname: Stillwell
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.forename: P L
authors.initials: PL
authors.lastname: Skipper
authors.forename: M C
authors.initials: MC
authors.lastname: Yu
authors.forename: R K
authors.initials: RK
authors.lastname: Ross
authors.forename: B E
authors.initials: BE
authors.lastname: Henderson
authors.forename: R J
authors.initials: RJ
authors.lastname: Turesky
authors.forename: G A
authors.initials: GA
authors.lastname: Gross
mesh_terms: D000328:Adult; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004041:Dietary Fats; D005006:Ethnicity; D006801:Humans; D008297:Male; D008460:Meat; D009153:Mutagens / Q000378:metabolism* / Q000493:pharmacokinetics; D011323:Primates; D011810:Quinoxalines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D051381:Rats
chemical_list: D002273:Carcinogens; D004041:Dietary Fats; D009153:Mutagens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline