Journal of Analytical Chemistry

, Volume 74, Issue 7, pp 722–727 | Cite as

Comparative Pharmacokinetics of Nootkatone in a RAT Model of Chronic Kidney Disease VERSUS Normal Controls

  • Yong-Hui LiEmail author
  • Pei-Pei Li
  • Yin-Feng TanEmail author
  • Hong-Die Cai
  • Xiao-Po Zhang
  • You-Bin Li
  • Jun-Qing Zhang


In this study, a simple, sensitive, and rapid analytical method was developed by ultra-performance liquid chromatography (UPLC) coupled with tandem quadrupole mass spectrometry (MS) for the determination of nootkatone in normal and chronic kidney disease (CKD) rat plasma using clarithromycin as internal standard. After sample preparation by simple liquid–liquid extraction, chromatography was performed on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 mm particle size) using gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1% (v/v) formic acid. Detection was achieved by electrospray ionisation MS under the multiple selective reaction monitoring mode. The linear range was 0.01‒500 ng/mL with the square regression coefficient (r) of 0.9975. The lower limit of quantification was 0.01 ng/mL. The intra- and inter-day precision was under 5% and the stability accuracy was between 3.6 and 7.0%. The average recoveries from spiked plasma samples were >83% and matrix effect was over 81%. The developed method was successfully applied to the pharmacokinetic study of nootkatone in normal and CKD rats after an oral administration of 50 mg/kg nootkaone. The results showed the cmax and area under curve of nootkaone were greatly decreased, meanwhile Vd/F and t1/2 were markedly increased in CKD rats. The pharmacokinetic characteristics of nootkatone in rats were significantly altered in CKD rats.


nootkatone CKD pharmacokinetics LC‒MS/MS 



This study was financially supported by the National Natural Science Foundation of China (81560738).


The authors declare no conflict of interest.


  1. 1.
    Li, W.B., Hu, C.J., Wu, S.S., Gao, Y., and Yu, L.Y., Chin. J. Exp. Tradit. Med. Formulae, 2013, vol. 19, no. 11, p. 261.Google Scholar
  2. 2.
    Ang Wang, Ben cao bei yao, Beijing: Traditional Chinese Medicine, 2009.Google Scholar
  3. 3.
    Jiang, B., Wang, W.J., Li, M.P., Huang, X.J., Huang, F., Gao, H., Sun, P.H., He, M.F., Jiang, Z.J., Zhang, X.Q., and Ye, W.C., Bioorg. Med. Chem. Lett., 2013, vol. 23, no. 13, p. 3879.CrossRefGoogle Scholar
  4. 4.
    Xu, J.J., Su, J., Li, Y., and Tan, N.H., Chem. Nat. Compd., 2013, vol. 49, no. 3, p. 457.CrossRefGoogle Scholar
  5. 5.
    Zhang, J.Q., Wang, Y., Li, Y.H., Lai, W.Y., Li, H.L., Duan, J.A., and Pei, L.X., Arch. Pharm. Sci. Res., 2012, vol. 35, p. 2143.CrossRefGoogle Scholar
  6. 6.
    Chen, F., Li, H.L., Tan, Y.F., Guan, W.W., Zhang, J.Q., Li, Y.H., Zhao, Y.S., and Qin, Z.M., Molecules, 2014, vol. 19, p. 4510.CrossRefGoogle Scholar
  7. 7.
    Chinese Pharmacopoeia, The State Pharmacopoeia Commission of PR China, Beijing: China Medical Science, 2010, vol. 3.Google Scholar
  8. 8.
    Li, W.B., Hu, C.J., Long, L.Y., Huang, Q.W., and Xie, X.Q., China J. Chin. Mater. Med., 2010, vol. 35, no. 24, p. 3278.Google Scholar
  9. 9.
    Li, Y.H., Tan, Y.F., Wei, N., and Zhang, J.Q., Afr. J. Tradit., Complementary Altern. Med., 2016, vol. 13, no. 5, p. 25.Google Scholar
  10. 10.
    Choia, H.J., Leea, J.H., and Junga, Y.S., Biochem. Biophys. Res. Commun., 2014, vol. 447, no. 2, p. 278.CrossRefGoogle Scholar
  11. 11.
    Kotanko, P., Carter, M., and Levin, N.W., Nephrol., Dial., Transplant., 2006, vol. 21, no. 8, p. 2057.CrossRefGoogle Scholar
  12. 12.
    Mariño, E., Clin. Transl. Immunol., 2016, vol. 5, no. 11, p. e107.CrossRefGoogle Scholar
  13. 13.
    Diwan, V., Mistry, A., Gobe, G., and Brown, L., J. Pharmacol. Toxicol. Methods, 2013, vol. 68, no. 2, p. 197.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  1. 1.Hainan Provincial Key Laboratory of R&D on Tropic Plants, Hainan Medical UniversityHaikouChina

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