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Liquid Extraction Surface Analysis (LESA) Electron-Induced Dissociation and Collision-Induced Dissociation Mass Spectrometry of Small Molecule Drug Compounds
Journal of the American Society for Mass Spectrometry ( IF 3.1 ) Pub Date : 2018-08-27 , DOI: 10.1007/s13361-018-2042-7
Andrea F. Lopez-Clavijo 1 , Rian L. Griffiths 1 , Richard J. A. Goodwin 2 , Helen J. Cooper 1
Affiliation  

Here, we present liquid extraction surface analysis (LESA) coupled with electron-induced dissociation (EID) mass spectrometry in a Fourier-transform ion cyclotron resonance mass spectrometer for the analysis of small organic pharmaceutical compounds directly from dosed tissue. First, the direct infusion electrospray ionisation EID and collision-induced dissociation (CID) behaviour of erlotinib, moxifloxacin, clozapine and olanzapine standards were compared. EID mass spectra were also compared with experimental or reference electron impact ionisation mass spectra. The results show that (with the exception of erlotinib) EID and CID result in complementary fragment ions. Subsequently, we performed LESA EID MS/MS and LESA CID MS/MS on singly charged ions of moxifloxacin and erlotinib extracted from a thin tissue section of rat kidney from a cassette-dosed animal. Both techniques provided structural information, with the majority of peaks observed for the drug standards also observed for the tissue-extracted species. Overall, these results demonstrate the feasibility of LESA EID MS/MS of drug compounds from dosed tissue and extend the number of molecular structures for which EID behaviour has been determined.

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中文翻译:

小分子药物化合物的液体萃取表面分析(LESA)电子诱导解离和碰撞诱导解离质谱

在这里,我们提出了一种在傅立叶变换离子回旋共振质谱仪中与电子诱导解离(EID)质谱联用的液体萃取表面分析(LESA)质谱仪,用于直接从给药组织中分析小型有机药物化合物。首先,比较了厄洛替尼,莫西沙星,氯氮平和奥氮平标准品的直接输注电喷雾电离EID和碰撞诱导解离(CID)行为。还将EID质谱图与实验或参考电子碰撞电离质谱图进行了比较。结果表明(厄洛替尼除外)EID和CID产生互补的碎片离子。随后,我们对从卡式给药动物的大鼠肾脏薄组织切片中提取的莫西沙星和厄洛替尼的单电荷离子进行了LESA EID MS / MS和LESA CID MS / MS。两种技术都提供了结构信息,对于药物标准品观察到的大多数峰也针对组织提取物进行了观察。总体而言,这些结果证明了来自剂量组织的药物化合物的LESA EID MS / MS的可行性,并扩展了已确定EID行为的分子结构的数量。

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更新日期:2018-08-27
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