Percutaneous Microdialysis and Pharmacokinetic Study of Tongluo-Qutong Rubber Plaster in Rats by UPLC-MS/MS

Percutaneous Microdialysis and Pharmacokinetic Study of Tongluo-Qutong Rubber Plaster in Rats by UPLC-MS/MS
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UPLC-MS/MS 经皮微透析及通络祛通橡皮膏在大鼠体内的药代动力学研究

DOI:
10.1177/1934578x20957826
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发表时间:
2020-09
影响因子:
1.8
通讯作者:
Liu Zhidong
Liu Zhidong
中科院分区:
医学4区
文献类型:
--
作者:
Pi Jiaxin;Zhang Ying;Ma Xutong;Wang Ping;Xiong Wei;Zhang Ludan;Liu Yiting;Qi Dongli;Li Nan;Guo Pan;Liu Zhidong

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通络祛痛橡胶膏(TQRP)是一种著名的用于治疗骨关节炎和颈椎病的中药方剂。由于缺乏体内渗透数据,TQRP的活性成分尚未完全阐明,这对TQRP临床应用的质量评估、药代动力学研究和安全性评估构成了巨大障碍。在本研究中,开发并验证了一种选择性好且重现性高的超高效液相色谱 - 串联质谱法,用于经皮微透析和药代动力学实验。在经皮微透析研究中,大黄素(EMO)和胡椒碱(PIP)的浓度 - 时间曲线下平均面积(AUC0 - 24h)分别为127.1和2603.6 h·ng/mL。在药代动力学研究中,测定了血浆样品中的阿魏酸(FA)、EMO和PIP。血浆中FA、EMO和PIP的平均AUC0 - 32h值分别为15441.5、202.0和1704.5 h·ng/mL。TQRP经皮给药后FA、EMO和PIP等活性成分的体内暴露水平为其生物活性成分的鉴定及其作用机制的进一步研究提供了思路和数据支持。
Tongluo-Qutong rubber plaster (TQRP) is a well-known traditional Chinese medicine prescription for the treatment of osteoarthritis and cervical spondylosis. Due to a lack of in vivo permeation data, the active ingredients of TQRP have not been fully elucidated, presenting a huge obstacle to quality evaluation, pharmacokinetic studies, and safety assessment of TQRP for clinical application. In this study, a selective and reproducible ultraperformance liquid chromatography tandem mass spectrometry method was developed and validated for percutaneous microdialysis and pharmacokinetic experiments. In the percutaneous microdialysis study, the mean area under the concentration–time curve (AUC0-24h) of emodin (EMO) and piperine (PIP) were 127.1 and 2603.6 h·ng/mL, respectively. In the pharmacokinetic study, ferulic acid (FA), EMO, and PIP were determined in plasma samples. The mean AUC0-32h.values of FA, EMO, and PIP in plasma were 15441.5, 202.0, and 1704.5 h·ng/mL, respectively. The in vivo exposure levels of active ingredients such as FA, EMO, and PIP after dermal administration of TQRP provide insights and data to support identification of its bioactive components and further study of its mechanism of action.
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