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超高效液相色谱-串联质谱法研究小鼠体内蝶啶的药代动力学及组织分布

Study on pharmacokinetics and tissue distribution of pteryxin in mice by ultra-pressure liquid chromatography with tandem mass spectrometry.

作者信息

Wang Juan, Ma Yufeng, Li Wen, Hu Fangdi, Chen Tongqiang, Shen Xiaoli, Feng Shilan

机构信息

School of Pharmacy, Lanzhou University, 199 Donggangxi Road, Lanzhou 730000, People's Republic of China.

出版信息

Biomed Chromatogr. 2012 Jul;26(7):802-7. doi: 10.1002/bmc.1733. Epub 2011 Nov 20.

Abstract

Pteryxin is a coumarin compound naturally occurring in the roots of Radix Peucedani, a commonly used as traditional Chinese medicine for the treatment of certain respiratory diseases and hypertension. An UPLC-MS/MS method was established to quantify pteryxin in mouse plasma and tissue homogenates. Isoimperatorin was used as internal standard (IS). The method was based on protein precipitation with methanol for sample preparation. Pteryxin and IS were separated using a UPLC™ BEH C₁₈ column and eluted with a mobile phase consisting of methanol and water (70:30, v/v) at a flow-rate of 0.2 mL/min. MS/MS detection was carried out by monitoring the fragmentation of m/z 409.3-287.2 for pteryxin and m/z 271.3-185.2 for IS on a triple-quadrupole mass spectrometer. The total run time was only 6 min. The results showed that it had good linearity over a wide concentration range (r > 0.999), and pteryxin was rapidly distributed and then eliminated from mouse plasma (t(½) =1.463 h). The major distribution tissues of pteryxin in mice were liver, and pteryxin was enabled to cross the blood-brain barrier owing to its low polarity. There was no long-term accumulation of pteryxin in mouse tissues.

摘要

翼藜素是一种香豆素化合物,天然存在于中药前胡的根部,前胡常用于治疗某些呼吸道疾病和高血压。建立了一种超高效液相色谱-串联质谱法(UPLC-MS/MS)来定量测定小鼠血浆和组织匀浆中的翼藜素。异欧前胡素用作内标(IS)。该方法基于用甲醇沉淀蛋白进行样品制备。翼藜素和内标采用UPLC™ BEH C₁₈色谱柱分离,以甲醇和水(70:30,v/v)为流动相,流速为0.2 mL/min进行洗脱。在三重四极杆质谱仪上通过监测翼藜素的m/z 409.3-287.2和内标的m/z 271.3-185.2的碎片进行串联质谱检测。总运行时间仅为6分钟。结果表明,该方法在较宽的浓度范围内具有良好的线性(r>0.999),翼藜素在小鼠血浆中快速分布然后消除(t(½)=1.463小时)。翼藜素在小鼠体内的主要分布组织为肝脏,由于其低极性,翼藜素能够穿过血脑屏障。翼藜素在小鼠组织中无长期蓄积现象。

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