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[采用超高效液相色谱-串联质谱法快速同时测定比格犬血浆中补骨脂果实的10种活性成分及其在药代动力学研究中的应用]

[Rapid and simultaneous determination of 10 active components of Psoraleae Fructus in beagle dog plasma using UPLC-MS/MS and its application in pharmacokinetic study].

作者信息

Wei Meng-Meng, Sun Xue-Yan, Wu Si-Yang, Wang Shu-Yao, Gao Yang, Kang Chen, Yang Wei, Li Ying-Fei, Li Chuan

机构信息

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences Shanghai 201203, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2021 Jan;46(2):444-453. doi: 10.19540/j.cnki.cjcmm.20200629.204.

Abstract

An UPLC-MS/MS method for rapid and simultaneous determination of psoralen, isopsoralen, apigenin, genistein, bavaisoflavone, neobavaisoflavone, bavachin, bavachinin, psoralenoside, and isopsoralenoside of Psoraleae Fructus in beagle dog plasma was established, and then the method was applied in the pharmacokinetic study after oral administration of Psoraleae Fructus extract to beagle dogs. The pharmacokinetic parameters were calculated by the software of WinNonlin. A Waters HSS-T3 column(2.1 mm×100 mm,1.8 μm)was used for liquid chromatography separation with acetonitrile-water(containing 0.004% formic acid) as the mobile phase for gradient elution.The mass spectrometry was detected using electrospray ion source(ESI) under multi-reaction monitoring mode(MRM), as well as positive ion mode. Analysis time only takes 8.5 min. The methodological study in terms of specificity, accuracy, precision, linear range, recovery, matrix effect, and stability, was validated. The LC-MS analysis method established in this experiment was simple, specific, accurate, reliable, and meet the requirement of pharmacokinetic study in plasma after administration of Psoraleae Fructus extract to beagle dogs. Six beagle dogs received intragastric administration of Psoraleae Fructus extract, T_(max) of 10 chemical components is 1.92-5.67 h; among them, C_(max) of psoralen, isopsoralen, psoralenoside and isopsoralenoside is 383-3 613 ng·mL(-1), and AUC_(0-∞) is 3 556-18 949 ng·h·mL(-1), t_(1/2) is 2.45-4.83 h. C_(max) of the remaining six compounds is 0.81-19.9 ng·mL(-1), AUC_(0-∞ )is 6.54-178 ng·h·mL(-1), t_(1/2) is 2.95-7.29 h. The UPLC-MS/MS analysis method established in this study was proved to be accurate and sensitive that it can be applied to the pharmacokinetic study of beagle dogs after oral administration of Psoraleae Fructus extract.

摘要

建立了一种超高效液相色谱 - 串联质谱法(UPLC-MS/MS),用于快速同时测定比格犬血浆中补骨脂果实中的补骨脂素、异补骨脂素、芹菜素、染料木黄酮、补骨脂异黄酮、新补骨脂异黄酮、补骨脂查尔酮、补骨脂宁、补骨脂苷和异补骨脂苷,然后将该方法应用于比格犬口服补骨脂果实提取物后的药代动力学研究。药代动力学参数通过WinNonlin软件计算。采用Waters HSS-T3柱(2.1 mm×100 mm,1.8 μm)进行液相色谱分离,以乙腈 - 水(含0.004%甲酸)为流动相进行梯度洗脱。质谱采用电喷雾离子源(ESI)在多反应监测模式(MRM)以及正离子模式下进行检测。分析时间仅需8.5分钟。对方法的特异性、准确性、精密度、线性范围、回收率、基质效应和稳定性等方面进行了方法学研究并验证。本实验建立的LC-MS分析方法简便、特异、准确、可靠,满足比格犬口服补骨脂果实提取物后血浆药代动力学研究的要求。6只比格犬灌胃给予补骨脂果实提取物,10种化学成分的T_(max)为1.92 - 5.67小时;其中,补骨脂素、异补骨脂素、补骨脂苷和异补骨脂苷的C_(max)为383 - 3613 ng·mL(-1),AUC_(0-∞)为3556 - 18949 ng·h·mL(-1),t_(1/2)为2.45 - 4.83小时。其余6种化合物的C_(max)为0.81 - 19.9 ng·mL(-1),AUC_(0-∞ )为6.54 - 178 ng·h·mL(-1),t_(1/2)为2.95 - 7.29小时。本研究建立的UPLC-MS/MS分析方法准确、灵敏,可应用于比格犬口服补骨脂果实提取物后的药代动力学研究。

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