University of Münster, Institute of Inorganic and Analytical Chemistry, 48149 Münster, Germany.
J Chromatogr A. 2012 Jun 1;1240:147-55. doi: 10.1016/j.chroma.2012.03.088. Epub 2012 Apr 3.
Oxidative and potentially metabolic pathways of the five most frequently used contrast agents for magnetic resonance imaging (MRI) based on gadolinium (Gd) are examined. The oxidation of gadopentetate (Gd-DTPA) was studied with a focus on electrochemical oxidation coupled to analytical separation methods and mass spectrometric detection. Mass voltammograms generated with online electrochemistry/electrospray ionization mass spectrometry (EC/ESI-MS) gave a first overview of oxidation products. Two potential metabolites could be detected, with the major metabolite originating from an N-dealkylation (M1). Four other Gd complexes used as MRI contrast agents showed similar reactions in the EC/ESI-MS set-up. To obtain more information about the properties and the quantity of the generated products, a wide range of separation and detection techniques was applied in further experiments. Gd-DTPA and its N-dealkylation product were successfully separated by capillary electrophoresis (CE) and detected by ESI-MS and inductively coupled plasma (ICP)-MS, respectively. CE experiments indicated that the second oxidation product (M2) detected in the mass voltammogram is unstable and decomposes to M1. Employing EC/CE/ICP-MS, the quantification of the metabolites could be achieved. Under the employed conditions, 8.8% of Gd-DTPA was oxidized. Online experiments with high performance liquid chromatography (HPLC) coupled to ESI-MS confirmed the decomposition of M2. Time-resolved measurements showed a decrease of M2 and a simultaneous increase in M1 within only a few minutes, confirming the conclusion that M2 degrades to M1, while EC/LC/ICP-MS measurements provided quantitative evidence as well. The EC/MS simulation shows that a metabolic transformation should not be disregarded in further research regarding the trigger of nephrogenic systemic fibrosis (NSF), a disease exclusively observed for several hundred dialysis patients after delivery of Gd-based MRI contrast agents with linear structure. Furthermore, the used methods may allow the prediction of options for the oxidative removal of these contrast agents from wastewaters.
检查了基于钆（Gd）的磁共振成像（MRI）中最常用的五种对比剂的氧化和潜在代谢途径。研究了戊二酸二葡甲胺（Gd-DTPA）的氧化，重点是电化学氧化与分析分离方法和质谱检测相结合。使用在线电化学/电喷雾电离质谱（EC/ESI-MS）生成的质谱伏安图提供了氧化产物的初步概述。可以检测到两种潜在的代谢产物，主要代谢产物源自 N-脱烷基化（M1）。作为 MRI 造影剂使用的其他四种 Gd 配合物在 EC/ESI-MS 装置中表现出相似的反应。为了获得有关生成产物的性质和数量的更多信息，在进一步的实验中应用了广泛的分离和检测技术。通过毛细管电泳（CE）成功地分离了 Gd-DTPA 和其 N-脱烷基化产物，并分别通过 ESI-MS 和电感耦合等离子体（ICP）-MS 进行检测。CE 实验表明，在质谱伏安图中检测到的第二个氧化产物（M2）不稳定，分解为 M1。采用 EC/CE/ICP-MS 可实现代谢产物的定量。在采用的条件下，Gd-DTPA 的氧化率为 8.8%。与 ESI-MS 耦合的高效液相色谱（HPLC）在线实验证实了 M2 的分解。时间分辨测量显示 M2 的减少和 M1 的同时增加仅在几分钟内，证实了 M2 降解为 M1 的结论，而 EC/LC/ICP-MS 测量也提供了定量证据。EC/MS 模拟表明，在进一步研究引发肾源性系统性纤维化（NSF）的触发因素时，不应忽略代谢转化，这种疾病仅在数百名接受线性结构的基于 Gd 的 MRI 造影剂的透析患者后观察到。此外，所使用的方法可能允许预测从废水中氧化去除这些造影剂的选择。
