Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization.
Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization.
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DOI：
10.1007/s00216-014-8220-y
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发表时间：
2015-03
影响因子：
4.3
通讯作者：
Muddiman, David C.
中科院分区：
文献类型：
--
作者：
Bokhart, Mark T.;Rosen, Elias;Thompson, Corbin;Sykes, Craig;Kashuba, Angela D. M.;Muddiman, David C.
关键词：
一种定量质谱成像（QMSI）技术，使用红外基质辅助激光解吸电喷雾电离（IR-MALDESI）证明了抗逆转录病毒（ARV）药物恩曲他滨在孵育的人宫颈组织。QMSI技术的方法开发导致几种抗逆转录病毒药物的灵敏度和干扰去除的增益。通过对几种阳离子化剂的详细评价，分析物响应显著改善。增加的灵敏度和同量异位素干扰的去除被证明与氯化钠在电喷雾溶剂。通过将分析物丰度标准化为具有与目标药物相似特征的均匀应用的化合物，改善了MSI实验的体素间变异性。最后，使用由稳定同位素标记的恩曲他滨类似物生成的校准曲线，然后使用液相色谱串联质谱法（LC-MS/MS）进行交叉验证，定量组织中的恩曲他滨。定量IR-MALDESI分析证明在恩曲他滨浓度为17.2±1.8 μg/g组织时具有重现性。该量对应于IR-MALDESI QMSI实验中7 fmol/体素的检测。使用LC-MS/MS分析相邻组织切片，得到恩曲他滨浓度为28.4±2.8 μg/g组织。
A quantitative mass spectrometry imaging (QMSI) technique using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is demonstrated for the antiretroviral (ARV) drug emtricitabine in incubated human cervical tissue. Method development of the QMSI technique leads to a gain in sensitivity and removal of interferences for several ARV drugs. Analyte response was significantly improved by a detailed evaluation of several cationization agents. Increased sensitivity and removal of an isobaric interference was demonstrated with sodium chloride in the electrospray solvent. Voxel-to-voxel variability was improved for the MSI experiments by normalizing analyte abundance to a uniformly applied compound with similar characteristics to the drug of interest. Finally, emtricitabine was quantified in tissue with a calibration curve generated from the stable isotope-labeled analog of emtricitabine followed by cross-validation using liquid chromatography tandem mass spectrometry (LC-MS/MS). The quantitative IR-MALDESI analysis proved to be reproducible with an emtricitabine concentration of 17.2±1.8 μg/gtissue. This amount corresponds to the detection of 7 fmol/voxel in the IR-MALDESI QMSI experiment. Adjacent tissue slices were analyzed using LC-MS/MS which resulted in an emtricitabine concentration of 28.4±2.8 μg/gtissue.
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DOI：
10.1016/j.vascn.2006.11.004
发表时间：
2007-05-01
影响因子：
1.9
作者：
Drexler, Dieter M.;Garrett, Timothy J.;Sanders, Mark
通讯作者：
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DOI：
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发表时间：
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影响因子：
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影响因子：
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作者：
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影响因子：
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