Profiling of sulfoconjugates in urine by using precursor ion and neutral loss scans in tandem mass spectrometry. Application to the investigation of heavy metal toxicity in rats
Profiling of sulfoconjugates in urine by using precursor ion and neutral loss scans in tandem mass spectrometry. Application to the investigation of heavy metal toxicity in rats
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DOI：
10.1002/jms.635
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发表时间：
2004-06-01
影响因子：
2.3
通讯作者：
Tabet, JC
中科院分区：
文献类型：
--
作者：
Lafaye, A;Junot, C;Tabet, JC
本文报道了一种液相色谱/电喷雾电离质谱（LC/ESI-MS）分析尿液中多种结构不同的硫缀合物的方法及其在大鼠尿液中重金属毒性生物标志物表征中的应用。首先采用固相萃取分离磺胺偶联物，然后在反相柱上进行液相色谱分离。通过同时监测80 a（或80 Th双荷离子）、m/z 80前驱体（SO3-）和m/z 97前驱体（HSO4-）的恒定损失，在三重四极杆质谱仪上检测了硫缀合物。优化了硫酸脱氢表雄酮和硫酸雌二醇的ESI-MS检测条件，并对其他硫缀合物进行了检测。利用所开发的方法对人类和大鼠的尿液样本进行分析，每种检测模式可检测到约15个峰。然后将其应用于大鼠重金属毒性的研究。对照和铀镉处理大鼠尿液的色谱指纹图谱对比分析显示，硫代偶联物的色谱图谱存在一些差异。诊断性的m/z比率通过分析个人尿液样本得到证实，其中一个观察到的变化似乎是铀毒性的特异性变化。通过将其色谱保留时间和碰撞诱导解离质谱（在四极离子阱仪器上进行的MS2和MS3）与合成化合物的质谱进行比较，确定了造成这种变化的离子为4-乙基苯酚硫酸盐。版权所有：John Wiley Sons， Ltd. 2004
This paper reports a liquid chromatographic/electrospray ionization mass spectrometric (LC/ESI-MS) method for profiling a wide range of structurally different sulfoconjugated compounds in urine and its application to the characterization of biomarkers for heavy metal toxicity in rat urine. Sulfoconjugates were first isolated by solid-phase extraction and the LC separation was performed on a reversed-phase column. Sulfoconjugates were detected in a triple-quadrupole mass spectrometer by simultaneously monitoring constant losses of 80 a (or 80 Th for doubly charged ions), precursors of m/z 80 (SO3-.) and precursors of m/z 97 (HSO4-). The ESI-MS detection conditions were optimized on dehydroepiandrosterone sulfate and estradiol sulfate and tested on other sulfoconjugates. The analysis of urine samples from humans and rats by using the developed method allowed the detection of about 15 peaks in each mode of detection. It was then applied to the investigation of heavy metal toxicity in rats. Comparative analysis of the chromatographic fingerprints of urine from control and uranium- and cadmium-treated rats showed several variations in the chromatographic pattern of the sulfoconjugates. Diagnostic m/z ratios were confirmed by analyzing individual urine samples and one of the observed variations seemed to be specific to uranium toxicity. The ion responsible for this variation has been identified as 4-ethylphenol sulfate by comparison of its chromatographic retention time and collision-induced dissociation mass spectra (MS2 and MS3 performed on a quadrupole ion trap instrument) with those of the synthesized compound. Copyright (C) 2004 John Wiley Sons, Ltd.