UPLC-MS/MS测定兔血浆中钩藤碱的浓度及在药代动力学中的应用

doi:10.5246/jcps.2015.06.050

中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (6): 393-399.DOI: 10.5246/jcps.2015.06.050

UPLC-MS/MS测定兔血浆中钩藤碱的浓度及在药代动力学中的应用

胡岚岚, 汤建林^*, 周世文

第三军医大学新桥医院临床药理基地重庆 400037

收稿日期:2014-12-31 修回日期:2015-01-29 出版日期:2015-06-26 发布日期:2015-02-21
通讯作者: Tel./Fax: 86-23-68755311

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

Lanlan Hu, Jianlin Tang^*, Shiwen Zhou

Base for Drug Clinical Trial, Xinqiao Hospital, the Third Military Medical University, Chongqing 400037, China

Received:2014-12-31 Revised:2015-01-29 Online:2015-06-26 Published:2015-02-21
Contact: Tel./Fax: 86-23-68755311

摘要/Abstract

摘要：

传统中药钩藤中主要的活性成分为钩藤碱。现代中药药理研究表明, 钩藤碱主要作用于心血管系统和中枢神经系统。关于钩藤碱在食草动物兔体内的药代动力学特征还未见报道, 由于临床前不同种属动物体内药代动力学研究对设计人体的药代学参数有重要意义, 所以本文采用对兔体内血药浓度的测定来研究钩藤碱的药代动力学, 并建立了快速灵敏的UPLC-MS/MS分析方法来测定血浆药物浓度。结果表明, 钩藤碱在0.01–10.24 µg/mL的浓度范围内呈线性, 日内、日间变异系数均小于8.0%, 相对回收率在94.17%–103.32%之间, 基质效应影响小。给兔灌胃三个剂量(20、40、80 mg/kg)的钩藤碱后, 血浆中的消除相t_1/2分别为1.19 h、1.49 h和1.37 h, 在20–80 mg/kg的剂量范围内曲线下的面积AUC_∞和达峰浓度C_max与给药剂量的线性呈正相关。所以本实验不仅可用于钩藤碱体内药代动力学研究, 也为设计和优化临床研究给药方案提供有关依据和参考。

关键词: 钩藤碱, 药代动力学, UPLC-MS/MS, 兔体内

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

中图分类号:

Supporting:

胡岚岚, 汤建林, 周世文. UPLC-MS/MS测定兔血浆中钩藤碱的浓度及在药代动力学中的应用[J]. 中国药学(英文版), 2015, 24(6): 393-399.

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.

参考文献

[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

UPLC-MS/MS测定兔血浆中钩藤碱的浓度及在药代动力学中的应用

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

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