caa a22 4500 445803150 CHVBK 20180317145148.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s10337-011-2068-5 doi (NATIONALLICENCE)springer-10.1007/s10337-011-2068-5 Analysis of 2-Amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine and Its Phase I and Phase II Metabolites in Mouse Urine Using LC-UV-MS-MS [Elektronische Daten] [S. Teunissen, H. Rosing, L. Brunsveld, T. de Greef, S. Durmus, J. Schellens, A. Schinkel, J. Beijnen] 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is an abundantly present heterocyclic aromatic amine which is found to be carcinogenic in rodents, mice and rats. The biotransformation of PhIP is extensive and involves both the formation of bioactivated as well as detoxification metabolites. In order to understand its carcinogenicity, the metabolism of PhIP needs to be studied. Numerous metabolites of PhIP have been described but, so far, assays for their quantitative determination in biological matrices are scarce. We present the development and application of an assay, using reversed phase liquid chromatography coupled to ultraviolet and mass spectrometry detectors for the quantification of PhIP, three phase I and nine phase II metabolites in urine. Additionally, the identification of two PhIP-sulfates by the use of NMR is presented. Sample pretreatment consisted of straightforward dilution of urine. PhIP and its metabolites were shown to be stable in diluted urine for at least 22h when stored at 2-8°C. Precision of the analysis was within 15%. The assay has been successfully applied for the quantification of PhIP and 12 of its metabolites in urine from mice that received 200mgkg−1 PhIP via oral gavage. Springer-Verlag, 2011 HPLC-UV-MS-MS, PhIP nationallicence Metabolites nationallicence Urine nationallicence Teunissen S. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands aut Rosing H. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands aut Brunsveld L. Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands aut de Greef T. Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands aut Durmus S. Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands aut Schellens J. Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands aut Schinkel A. Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands aut Beijnen J. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands aut Chromatographia Springer-Verlag 74/3-4(2011-08-01), 215-226 0009-5893 74:3-4<215 2011 74 10337 https://doi.org/10.1007/s10337-011-2068-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10337-011-2068-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Teunissen S. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Rosing H. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Brunsveld L. Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands aut NATIONALLICENCE 700 1- de Greef T. Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands aut NATIONALLICENCE 700 1- Durmus S. Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Schellens J. Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Schinkel A. Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Beijnen J. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands aut NATIONALLICENCE 773 0- Chromatographia Springer-Verlag 74/3-4(2011-08-01), 215-226 0009-5893 74:3-4<215 2011 74 10337 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer