کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5136457 | 1494015 | 2017 | 12 صفحه PDF | دانلود رایگان |
- Metabolism of 2-amino-9H-pyrido[2,3-b]indole was first investigated by UPLC-TOF-MS/MS.
- Metabolic profiles of AαC in four liver microsomes and rat urine were investigated.
- 9 metabolites (including two new quinone metabolites) have been found in vitro.
- 23 metabolites (including five new N-acetyl-AαC-OH) were identified in rat urine.
2-Amino-9H-pyrido[2,3-b]indole (AαC), which has been reported to be 40-258 ng per cigarette, was regarded as a probable human carcinogen (Group 2B) and harmful composition in Hoffman list. Thus, it is of great significance to develop an effective method for the accurate identification of AαC and its metabolites. In the present study, we have investigated for the first time the in vivo and in vitro metabolites of AαC using ultra performance liquid chromatography combined with diode array detector and time-of-flight mass spectrometry (UPLC-DAD and UPLC-Q-TOF-MS/MS). A comparative study showed that the metabolic patterns of AαC in beagle, mouse, rat and human liver microsomes were of significant difference with these in rat urine. For the metabolism of AαC in liver microsomes, nine metabolites of AαC, including five hydroxy metabolites, two quinone metabolites and two N-dimer metabolites, have been found. However, metabolism of AαC in rats is a phase II process with complex enzyme catalysis, 23 metabolites including C- and N-oxidation, O- and N-glycosylation, O- and N-sulfonation, and N-acetylation were identified in rat urine. In addition, five new N-acetyl-AαC-OH metabolites were identified for the first time, indicating a possible new pathway for the metabolism. This study significantly enriched our knowledge about the metabolism of AαC, and will be useful for a better understanding of its harmfulness and toxicity.
Journal: Journal of Chromatography B - Volume 1046, 1 March 2017, Pages 110-121