Quantification of rhynchophylline in rabbit plasma by UPLC-MS/MS and its application in a pharmacokinetic study

doi:10.5246/jcps.2015.06.050

Abstract

Abstract:

It was recently revealed thatRhynchophylline (Rhy), an important constituent of Uncaria rhynchophylla, possessed antihypertensive and neuroprotective effects. However, no information about the pharmacokinetics of Rhy in a herbivorous speciessuch as rabbit is available. Allometric scaling is valuable in designing human pharmacokinetic parameters from preclinical species. To investigate the characteristics of Rhy in vivo, a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the measurement of Rhy concentrations in rabbit plasma. The method was linear over the concentration range of 0.01–10.24 µg/mL. Intra-day and inter-day precision and accuracy were less than 8.0%. The recoveries were in the range of 94.17%–103.32%. Matrix effects (ME) were minor. After oral administration of Rhy at 20, 40 and 80 mg/kg, the mean elimination half-life (t_1/2) for these doses were 1.19, 1.49 and 1.37 h in rabbits, respectively. There was a proportionate increase in the maximum concentration (C_max) and the area under the blood concentration-time curve (AUC_∞) for three doses. The developed method was suitable for the study on pharmacokinetics of Rhy after oral administration and it may provide a valuable basis for clinical application of such a bioactive compound of herbal medicines.

Key words: Rhynchophylline, Pharmacokinetics, UPLC-MS/MS, In rabbit

CLC Number:

Supporting:

Lanlan Hu, Jianlin Tang, Shiwen Zhou. Quantification of rhynchophylline in rabbit plasma by UPLC-MS/MS and its application in a pharmacokinetic study[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(6): 393-399.

References

[1] Zhou, J.Y.; Zhou, S.W. J. Ethnopharmacol. 2010, 132, 15-27.

[2] Ho, T.Y.; Tang, N.Y.; Hsiang, C.Y.; Hsieh, C.L. Phyto-medicine. 2014, 6, 893-900.

[3] Liu,W.; Peng, Q.X.; Lin X.L.; Luo, C.H.; Jiang, M.J.; Mo, Z.X.; Yung, K.K.L. Fitoterapia. 2014, 92, 16-22.

[4] Lin, Y.W.; Hsieh, C.L. J. Ethnopharmacol. 2011, 2, 313-320.

[5] Mohamed, A.F.; Matsumoto, K.; Tabata, K.; Takayama, H.; Kitajima, M.; Watanabe, H. J. Pharm. Pharmacol. 2000, 52, 1553-1561.

[6] Zhang, W.B.; Chen, C.X.; Sim, S.M.; Kwan, C.Y. Naunyn Schmiedeberg’s Arch. Pharmacol. 2004, 369, 232-238.

[7] Chou, C.H.; Gong, C.L.; Chao, C.C.; Lin, C.H.; Kwan, C.Y.; Hsieh, C.L.; Leung, Y.M. J. Nat. Prod. , 72, 830-834.2009

[8] Hsieh, C.L.; Ho, T.Y.; Su, S.Y.; Lo, W.Y.; Liu, C.H.; Tang, N.Y. Am. J. Chin. Med. 2009, 37, 351-360.

[9] Yuan, D.; Ma, B.; Yang, J.Y.; Xie, Y.Y.; Wang, L.; Zhang, L.J.; Kano, Y.; Wu, C.F. Int. Immunopharmacol. 2009, 9, 1549-1554.

[10] Amat, M.; Ramos, C.; Prez, M.; Molins, E.; Florindo, P.; Santos, M.M. Chem. Commun. (Camb). 2013, 49, 1954-1956.

[11] Zhou, J.Y.; Chen, J.; Zhou, S.W.; Mo, Z.X. Fitoterapia. 2013, 85, 125-129.

[12] Zhou, J.Y.; Zhou, S.W. Fitoterapia. 2012, 83, 617-626.

[13] Song, Y.; Qu, R.; Zhu, S.; Zhang, R.; Ma, S. Phytother. Res. 2012, 26, 1528-1533.

[14] Cao, W.J.; Wang, Y.; Lv, X.X.; Yu, X.H.; Li, X.J.; Li, H.M.; Wang, Y.P.; Lu, D.X.; Qi, R.B.; Wang, H.D. Int. Immunopharmacol. 2012, 14, 243-251.

[15] Lv, G.Y.; Lou, Z.H.; Chen, S.H.; Gu, H.; Shan, L.T. J. Ethnopharmacol. 2011, 137, 449-456.

[16] Wang, W.; Ma, C.M.; Hattori, M. Biol. Pharm. Bull. 2010, 33, 669-676.

[17] Ma, B.; Sun, G.B.; Xu, H.B.; Li, M.; Yang, Z.H.; Sun, X.B. J. Med. Plants Res. 2012, 6, 2977-2984.

[18] US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for Industry, Bioanalytical Method Validation. 2001.

[19] Oldekop, M.L.; Herodes, K.; Rebane, R. J. Chromatogr. B. 2014, 967, 147-155.

[20] Davies, B.; Morris, T. Pharmaceut. Res. , 10, 1093-1095.1993