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一种灵敏的 UHPLC-MS/MS 法同时定量测定人血浆中的三种木脂素及其在药代动力学研究中的应用。

A sensitive UHPLC-MS/MS method for the simultaneous quantification of three lignans in human plasma and its application to a pharmacokinetic study.

机构信息

Department of Pharmacy, College of Pharmacy and Institue of Pharmaceutical Sciences, CHA University, Seongnam-si, Republic of Korea.

National Development Institute of Korean Medicine, Jangheung-gun, Republic of Korea.

出版信息

J Sep Sci. 2017 Sep;40(17):3430-3439. doi: 10.1002/jssc.201700588. Epub 2017 Aug 4.

Abstract

The aim of this study was to develop an analytical method to simultaneously analyze schizandrin, schizandrol B, and gomisin N lignans in human plasma using ultra high performance liquid chromatography with tandem mass spectrometry. The three lignans were separated using a mobile phase of water and acetonitrile containing 0.02% acetic acid equipped with a Kinetex C column (2.1 mm × 50 mm, 1.7 μm). This analysis was achieved by multiple reaction monitoring mode in an electrospray interface. The mass transitions were m/z 433.1→384.0 for schizandrin, 398.8→367.8 for schizandrol B, and 400.6→299.8 for gomisin N. Liquid-liquid extraction with methyl tert-butyl ether was used to obtain the three lignans. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. The calibration curves for the three lignans in human plasma were 0.05-50 ng/mL and displayed excellent linearity with correlation coefficients greater than 0.99. Precision for all three lignans was within 11.23%. The accuracy was 88.3-99.0% for schizandrin, 90.6-103.4% for schizandrol B, and 90.2-103.5% for gomisin N. The developed simultaneous analytical method satisfied the criteria of international guidance and could be successfully applied to the pharmacokinetic study of three lignans after oral administration of Schisandrae Fructus extract powder to humans.

摘要

本研究旨在开发一种分析方法,采用超高效液相色谱-串联质谱法同时分析人血浆中的五味子甲素、五味子醇 B 和戈米辛 N 木脂素。三种木脂素采用水和含 0.02%乙酸的乙腈作为流动相,在 Kinetex C 柱(2.1mm×50mm,1.7μm)上分离。该分析通过电喷雾接口的多反应监测模式实现。质荷比转换分别为 m/z 433.1→384.0 用于五味子甲素,398.8→367.8 用于五味子醇 B,400.6→299.8 用于戈米辛 N。采用甲基叔丁基醚进行液-液萃取获得三种木脂素。色谱图显示出高分辨率、灵敏度和选择性,无血浆成分干扰。三种木脂素在人血浆中的校准曲线为 0.05-50ng/mL,具有优异的线性关系,相关系数均大于 0.99。所有三种木脂素的精密度均在 11.23%以内。五味子甲素的准确度为 88.3-99.0%,五味子醇 B 的准确度为 90.6-103.4%,戈米辛 N 的准确度为 90.2-103.5%。所开发的同时分析方法符合国际指南的标准,可成功应用于口服五味子提取物粉末后三种木脂素的药代动力学研究。

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