Stereoselective pharmacokinetic study of rhynchophylline and isorhynchophylline epimers in rat plasma by liquid chromatography-tandem mass spectrometry
Stereoselective pharmacokinetic study of rhynchophylline and isorhynchophylline epimers in rat plasma by liquid chromatography-tandem mass spectrometry
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液相色谱-串联质谱法研究大鼠血浆中钩藤碱和异钩藤碱差向异构体的立体选择性药代动力学
DOI：
10.1080/00498254.2016.1203043
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发表时间：
2017
期刊：
影响因子：
1.8
通讯作者：
Feng Feng
中科院分区：
文献类型：
--
作者：
Wang Xin;Zheng Mei;Liu Jia;Qiao Zhou;Liu Wenyuan;Feng Feng
1.本研究采用液相色谱-串联质谱（LC-MS /MS）技术研究了铃兰碱（RIN）和异铃兰碱（IRN）在大鼠血浆中的立体选择性药代动力学。建立了一种快速、可靠、灵敏的LC-MS /MS同时定量大鼠血浆中RIN和IRN的方法。色谱柱为Poroshell 120 ec - c18，以含0.01%氨的甲醇和水为流动相，梯度洗脱。在1 ~ 2000 ng/mL的浓度范围内，两种外显物的校准曲线均呈线性。经静脉给药后，两种药代动力学参数无明显差异。然而，口服给药后，RIN的血浆暴露量明显高于IRN。10 mg/kg时，RIN的生物利用度、cmax和AUC0-tof分别是IRN的9.2倍、6.4倍和9.1倍；20 mg/kg时，RIN的生物利用度、cmax和AUC0-tof分别是IRN的7.8倍、4.3倍和7.7倍。此外，当剂量从10 mg/kg增加到20 mg/kg时，血浆中RIN或IRN浓度显著升高，生物利用度提高约3倍。综上所述，本研究结果首次证明了RIN和IRN的药代动力学具有立体选择性。
1. In this study, the stereoselective pharmacokinetics of rhynchophylline (RIN) and isorhynchophylline (IRN) in rat plasma were investigated using liquid chromatography–tandem mass spectrometry (LC–MS/MS).2. A rapid, robust and sensitive LC–MS/MS method for simultaneous quantification of RIN and IRN in rat plasma was established and validated. Chromatographic separation was performed on a Poroshell 120 EC-C18column under a gradient elution with methanol and water containing 0.01% ammonia as mobile phase. Calibration curve was linear over a concentration range of 1–2000 ng/mL for both epimers.3. After intravenous administration, there was no apparent difference in pharmacokinetic parameters between two epimers. However, after oral administration, RIN showed remarkable higher plasma exposure than IRN. The bioavailability,Cmaxand AUC0–tof RIN were about 9.2-fold, 6.4-fold and 9.1-fold higher than those of IRN at 10 mg/kg, and 7.8-fold, 4.3-fold and 7.7-fold at 20 mg/kg, respectively. Additionally, with dosage enhanced from 10 mg/kg to 20 mg/kg, the plasma concentrations of RIN or IRN increased significantly and the bioavailability enhanced about three times.4. In conclusion, the results of this work demonstrated for the first time that the pharmacokinetics of RIN and IRN have stereoselectivity.