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采用超高效液相色谱-电喷雾电离四极杆-飞行时间质谱法研究四君子汤灌胃给药后在大鼠血浆中的药代动力学。

Pharmacokinetics of Sijunzi decoction in rat plasma after oral administration using ultra-high-performance liquid chromatography electrospray ionization quadrupole-time of flight mass spectrometry.

作者信息

Qu Gonglin, Qi Xuesong, Shao Shuai, Li Chen, Wang Chunyan, Wang Chengfang, Gou Qiao

机构信息

China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, China.

出版信息

Biomed Chromatogr. 2018 Nov;32(11):e4334. doi: 10.1002/bmc.4334. Epub 2018 Aug 23.

DOI:10.1002/bmc.4334
PMID:29993133
Abstract

Sijunzi decoction (SJZD) is one of the most well-known traditional Chinese herbal formulations. This study elucidates the pharmacokinetics of SJZD in rat plasma after the administration of a single oral dose of 3 mL/kg using ultra-high-performance liquid chromatography electrospray ionization quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS) with bergapten as an internal standard. The separation was performed on an Agilent Zorbax Eclipse Plus C column (2.1 × 50 mm, 1.8 μm) by elution with acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. Electrospray ionization in positive and negative ion modes was used to quantify six compounds, with monitored ion m/z values of 249.1397 [M + H] and 529.3857 [M + H] for atractylenolide III (ATL-III) and pachymic acid (PA), respectively, and m/z of 1107.6638 [M - H] , 991.5746 [M - H + HCOO] , 821.3714 [M - H] , 469.3315 [M - H] for ginsenoside Rb Re, glycyrrhizic acid (GL), and glycyrrhetinic acid (GA), respectively. The calibration curves for ginsenoside Rb , Re, ATL-III, PA, GL and GA were 0.0015-0.75, 0.001-0.5, 0.0004-0.2, 0.003-0.9, 0.0015-0.3 and 0.001-1.5 μg/mL, respectively. The intra- and inter-day precisions (RSD) were <14.3%. The rapid, sensitive and specific UHPLC-ESI-Q-TOF/MS method developed and validated in this study was successfully applied to the simultaneous determination of the six components of SJZD using rat plasma for pharmacokinetic studies after oral administration.

摘要

四君子汤(SJZD)是最著名的传统中药配方之一。本研究采用超高效液相色谱电喷雾电离四极杆飞行时间质谱(UHPLC-ESI-Q-TOF/MS),以补骨脂素为内标,阐明了大鼠单次口服3 mL/kg剂量后SJZD在大鼠血浆中的药代动力学。在Agilent Zorbax Eclipse Plus C柱(2.1×50 mm,1.8μm)上进行分离,以乙腈和水(含0.1%甲酸)为流动相,流速为0.3 mL/min。采用正离子和负离子模式的电喷雾电离对6种化合物进行定量,白术内酯III(ATL-III)和茯苓酸(PA)的监测离子m/z值分别为249.1397 [M + H]和529.3857 [M + H],人参皂苷Rb1、Re、甘草酸(GL)和甘草次酸(GA)的m/z值分别为1107.6638 [M - H]、991.5746 [M - H + HCOO]、821.3714 [M - H]、469.3315 [M - H]。人参皂苷Rb1、Re、ATL-III、PA、GL和GA的校准曲线分别为0.0015 - 0.75、0.001 - 0.5、0.0004 - 0.2、0.003 - 0.9、0.0015 - 0.3和0.001 - 1.5μg/mL。日内和日间精密度(RSD)均<14.3%。本研究建立并验证的快速、灵敏、特异的UHPLC-ESI-Q-TOF/MS方法成功应用于口服给药后大鼠血浆中SJZD六种成分的同时测定,用于药代动力学研究。

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