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  • P-ISSN 1225-0163
  • E-ISSN 2288-8985

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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

    Analytical Science and Technology / Analytical Science and Technology, (P)1225-0163; (E)2288-8985
    2015, v.28 no.2, pp.132-138
    https://doi.org/10.5806/AST.2015.28.2.132





    SHINYOUNG GEUN
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    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


    Reference

    1

    1. J. M. Lehmann, L. B. Moore, T. A. Smitholiver, W. O. Wilkison, T. M. Willson and S. A. Kliewer, J. Biol. Chem., 270(22), 12953-12956 (1995).

    2

    2. A. R. Saltiel and J. M. Olefsky, Diabetes, 45(12), 1661-1669 (1996).

    3

    3. J. Kohlroser, J. Mathai, J. Reichheld, B. F. Banner and H. L. Bonkovsky, Am. J. Gastroenterol, 95(1), 272-276 (2000).

    4

    4. K. V. N. Menon, P. Angulo and K. D. Lindor, Am. J. Gastroenterol, 96(5), 1631-1634 (2001).

    5

    5. R. Alvarez-Sanchez, F. Montavon, T. Hartung and A. Pahler, Chem. Res. Toxicol., 19(8), 1106-1116 (2006).

    6

    6. S. L. Pearson, M. A. Cawthorne, J. C. Clapham, S. J. Dunmore, S. D. Holmes, G. B. T. Moore, S. A. Smith and M. Tadayyon, Bioche. Biophys. Res. Commun., 229(3), 752-757 (1996).

    7

    7. R. Alvarez-Sanchez, F. Montavon, T. Hartung and A. Pahler, Chem. Res. Toxicol., 19(8), 1106-1116 (2006).

    8

    8. P. J. Cox, D. A. Ryan, F. J. Hollis, A. M. Harris, A. K. Miller, M. Vousden and H. Cowley, Drug Metab. Disposit., 28(7), 772-780 (2000).

    9

    9. A. Aghazadeh-Habashi, A. Ibrahim, J. Carran, T. Anastassiades and F. Jamali, J. Pharm. Sci., 9(3), 359-364 (2006).

    10

    10. C. E. C. A. Hop, Z. Wang, Q. Chen and G. Kwei, J. Pharm. Sci., 87(7), 901-903 (1998).

    11

    11. M. Uchiyama, H. Iwabuchi, F. Tsuruta, K. Abe, M. Takahashi, H. Koda, M. Oguchi, O. Okazaki and T. Izumi, Drug Metab. Disposi., 39(4), 653-666 (2011).

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