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

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（英文）

作　　者：胡岚岚[1] 汤建林[1] 周世文[1] 

机构地区：[1]第三军医大学新桥医院临床药理基地,重庆400037

出　　处：《Journal of Chinese Pharmaceutical Sciences》2015年第6期393-399,共7页中国药学（英文版）

摘　　要：It was recently revealed that Rhynchophylline （Rhy）, an important constituent of Uncaria rhynchophylla, possessed antihypertensive and neuroprotective effects. However, no information about the pharmacoldnetics of Rhy in a herbivorous species such 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 （h/E） for these doses were 1.19, 1.49 and 1.37 h in rabbits, respectively. There was a proportionate increase in the maximum concentration （Cmax） 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.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0.01–10.24μg/m L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t1/2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Cmax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：RHYNCHOPHYLLINE PHARMACOKINETICS UPLC-MS/MS In rabbit 

分 类 号：R285.5[医药卫生—中药学]