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Comparison of rosiglitazone metabolite profiles in rat plasma between intraperitoneal and oral administration and identifcation of a novel metabolite by liquid chromatography-triple time of flight mass spectrometry

액체크로마토그라피-삼중비행시간질량분석기를 사용한 rosiglitazone의 복강 및 경구투여 후 대사체 비교 분석

  • Received : 2014.08.18
  • Accepted : 2015.03.23
  • Published : 2015.04.25

Abstract

Rosiglitazone metabolites in rat plasma were analyzed after intraperitoneal and oral administration to rats. Seven metabolites (M1-M7) were detected in rat plasma (IP and PO), and the structures were confirmed using liquid chromatography-triple time of flight (TOF) mass spectrometry; as a result, the most abundant metabolite was M5, a de-methylated rosiglitazone. Other minor in vivo metabolites were driven from monooxygenation and demethylation (M2), thiazolidinedione ring-opening (M1, M3), mono-oxygenation (M4, M7), and mono-oxygenation followed by sulfation (M6). Among them, M1 was found to be a 3-{p-[2-(N-methyl-N-2-pyridylamino)ethoxy]phenyl}-2-(methylsulfinyl)propionamide, which is a novel metabolite of rosiglitazone. There was no significant difference in the metabolic profiles resulting from the two administrations. The findings of this study provide the first comparison of circulating metabolite profiles of rosiglitazone in rat after IP and PO administration and a novel metabolite of rosiglitazone in rat plasma.

Keywords

Rosiglitazone;Triple time of flight mass spectrometer;Metabolic profile

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