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Human exposure to heterocyclic aromatic amines such as MeIQx (2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline) may be monitored by measuring the levels of the heterocyclic aromatic amine in urine. In order to investigate the contribution of N -oxidation to the metabolism of MeIQx in vivo, we developed a biomonitoring procedure for the analysis and quantification of the N 2 -glucuronide conjugate of 2-hydroxyamino-3,8-dimethylimidazo[4,5- f ]quinoxaline in human urine. Subjects ( n=66 ) in the dietary study ingested a uniform diet of cooked meat containing known amounts of MeIQx, and urine was collected after consumption of the test meal. A method based on solid-phase extraction and immunoaffinity separation was used to isolate N 2 -(β-1-glucosiduronyl)-2-hydroxyamino-3,8-dimethylimidazo[4,5- f ]quinoxaline and its stable isotope-labeled internal standard from urine. The isolated conjugate was converted to the deaminated product 2-hydroxy-3,8-dimethylimidazo[4,5- f ]quinoxaline by treatment with acetic acid under moderate heating. 2-Hydroxy-3,8-dimethylimidazo[4,5- f] quinoxaline and the [ 2 H 3 ]methyl analog were derivatized to form the corresponding 3,5- bis (trifluoromethyl)benzyl ether derivatives and quantified by capillary gas chromatography–negative ion chemical ionization mass spectrometry employing selected ion monitoring procedures. The amounts of N 2 -(β-1-glucosiduronyl)-2-hydroxyamino-3,8-dimethylimidazo[4,5- f ]quinoxaline recovered in urine collected 0–12 h after the test meal accounted for 2.2–17.1% of the ingested dose, with a median value of 9.5%. The variability in the proportion of the dose excreted among the subjects may be reflective of several factors, including interindividual variation in the enzymic activity of CYP1A2 and/or conjugation reactions of the N -hydroxylamine metabolite with N -glucuronosyltransferase(s). |
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