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用于检测薄组织切片中药物和代谢物的液体微通道表面采样探针电喷雾质谱法。

Liquid microjunction surface sampling probe electrospray mass spectrometry for detection of drugs and metabolites in thin tissue sections.

作者信息

Van Berkel Gary J, Kertesz Vilmos, Koeplinger Kenneth A, Vavrek Marissa, Kong Ah-Ng Tony

机构信息

Organic and Biological Mass Spectrometry Group, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6131, USA.

出版信息

J Mass Spectrom. 2008 Apr;43(4):500-8. doi: 10.1002/jms.1340.

DOI:10.1002/jms.1340
PMID:18035855
Abstract

A self-aspirating, liquid microjunction surface sampling probe/electrospray emitter mass spectrometry system was demonstrated for use in the direct analysis of spotted and dosed drugs and their metabolites in thin tissue sections. Proof-of-principle sampling and analysis directly from tissue without the need for sample preparation was demonstrated first by raster scanning a region on a section of rat liver onto which reserpine was spotted. The mass spectral signal from selected reaction monitoring was used to develop a chemical image of the spotted drug on the tissue. The probe was also used to selectively spot sample areas of sagittal whole-body tissue from a mouse that had been dosed orally (90 mg/kg) with R,S-sulforaphane 3 h prior to sacrifice. Sulforaphane and its glutathione and N-acetyl cysteine conjugates were monitored with selected reaction monitoring and detected in the stomach and various other tissues from the dosed mouse. No signal for these species was observed in the tissue from a control mouse. The same dosed-tissue section was used to illustrate the possibility of obtaining a lane scan across the whole-body section. In total, these results illustrate the potential for rapid screening of the distribution of drugs and metabolites in thin tissue sections with the liquid micro-junction surface sampling probe/electrospray mass spectrometry approach. Published in 2007 by John Wiley & Sons, Ltd.

摘要

一种自吸式液体微通道表面采样探针/电喷雾发射器质谱系统被证明可用于直接分析薄组织切片中斑点状和给药后的药物及其代谢物。首先通过对大鼠肝脏切片上利血平斑点所在区域进行光栅扫描,证明了无需样品制备即可直接从组织进行原理验证采样和分析。选定反应监测的质谱信号用于生成组织上斑点药物的化学图像。该探针还用于选择性地对一只在处死前3小时口服(90毫克/千克)R,S-萝卜硫素的小鼠的矢状全身组织的样品区域进行斑点分析。通过选定反应监测对萝卜硫素及其谷胱甘肽和N-乙酰半胱氨酸缀合物进行监测,并在给药小鼠的胃和其他各种组织中检测到。在对照小鼠的组织中未观察到这些物质的信号。同一给药组织切片用于说明在全身切片上进行泳道扫描的可能性。总的来说,这些结果说明了利用液体微通道表面采样探针/电喷雾质谱方法快速筛选薄组织切片中药物和代谢物分布的潜力。由约翰·威利父子有限公司于2007年出版。

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