Qualitative-(semi)quantitative data acquisition of artemisinin and its metabolites in rat plasma using an LTQ/Orbitrap mass spectrometer
Qualitative-(semi)quantitative data acquisition of artemisinin and its metabolites in rat plasma using an LTQ/Orbitrap mass spectrometer
复制标题
使用 LTQ/Orbitrap 质谱仪采集大鼠血浆中青蒿素及其代谢物的定性（半）定量数据
DOI：
10.1002/jms.2958
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发表时间：
2012-02-01
影响因子：
2.3
通讯作者：
Xing, Jie
中科院分区：
文献类型：
--
作者：
Du, Fuying;Liu, Tian;Xing, Jie
青蒿素（QHS）是一线抗疟药之一，CYP介导的代谢的自身诱导可导致其暴露减少。为了更好地了解QHS的自诱导，我们使用液相色谱-高分辨率质谱（LC-HRMS）方法评价了QHS及其I相代谢产物在大鼠体内的药代动力学。改进了LC分离，使QHS及其代谢物与其非对映体分离，并在大鼠血浆中鉴定了7种暴露量相对较高的QHS代谢物，包括脱氧青蒿素（DQHS）、3种单羟基加脱氧代谢物（M1 M3）和3种单羟基代谢物（M4 M6）。对于检测，使用具有正离子模式的电喷雾电离（ESI）入口的高分辨率LTQ/Orbitrap质谱仪。每个分析物的高分辨率提取的离子色谱图，通过处理全扫描MS数据集与10？ppm质量公差。血浆样品用乙腈沉淀蛋白质进行预处理。在50 μ l血浆中，QHS和DQHS的浓度在5.0200.0ng/ml范围内呈良好的线性关系（r ~ 2>0.99），为QHS及其代谢物的测定提供了足够的灵敏度和准确度。采用3天验证方法对QHS和DQHS进行绝对定量。根据QHS的校准曲线，对QHS的其他6种代谢产物进行半定量。将本方法应用于大鼠单次口服QHS后的药代动力学研究。这里显示的数据还表明，这种类型的质量分析仪将能够进行定量均衡的工作流程。版权所有（C）2012约翰威利父子有限公司
Artemisinin (QHS) is one of the first-line antimalarials, and autoinduction of CYP-mediated metabolism can result in its reduced exposure. To better understand the autoinduction of QHS, we evaluated the pharmacokinetics of QHS and its phase I metabolites in rats using an liquid chromatography-high resolution mass spectrometry (LC-HRMS) method. The LC separation was improved, allowing the separation of QHS and its metabolites from their diastereomers, and seven metabolites of QHS with relatively high exposure were identified in rat plasma, including deoxyartemisinin (DQHS), three monoyhydroxylated plus deoxyl metabolites (M1M3) and three monohydroxylated metabolites (M4M6). For detection, a high-resolution LTQ/Orbitrap mass spectrometer with an electrospray ionization (ESI) inlet in the positive ion mode was used. High-resolution extracted ion chromatograms for each analyte were obtained by processing the full-scan MS dataset with 10?ppm mass tolerance. The plasma samples were pretreated by protein precipitation with acetonitrile. The standard curve was linear (r2>0.99) over the QHS and DQHS concentration range of 5.0200.0ng/ml in 50 mu l of plasma, which offered sufficient sensitivity and accuracy for the determination of QHS and its metabolites. A 3-day validation approach was used for absolute quantitation of QHS and DQHS. The other six metabolites of QHS were semiquantified based on the calibration curve of QHS. The present method was applied to the pharmacokinetic study of QHS in rats after a single oral administration. The data shown here also suggest that this type of mass analyzer will be capable of a quantitativequalitative workflow. Copyright (C) 2012 John Wiley & Sons, Ltd.