Künnemeyer Jens, Terborg Lydia, Nowak Sascha, Telgmann Lena, Tokmak Faruk, Krämer Bernhard K, Günsel Andreas, Wiesmüller Gerhard A, Waldeck Jens, Bremer Christoph, Karst Uwe
Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstrasse 30, 48149 Münster, Germany.
Anal Chem. 2009 May 1;81(9):3600-7. doi: 10.1021/ac8027118.
To study transmetalation effects of the gadolinium-based contrast agent Magnevist (Gd-DTPA), the first analytical method for the simultaneous determination of Gd-DTPA and its transmetalation products in complex clinical samples was developed. The high separation efficiency of capillary electrophoresis (CE) was employed to separate Gd-DTPA, Fe-DTPA, Cu-DTPA, Zn-DTPA, and the free DTPA (diethylenetriaminepentaacetic acid) ligand. The coupling of CE with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) provided the required sensitivity and excellent selectivity for the analysis of complex samples, such as blood plasma and whole blood. Separation and detection parameters were optimized, and crucial steps for CE/MS method development are pointed out. Limit of detection (LOD) is 5 x 10(-7) mol/L, limit of quantification (LOQ) is 1.7 x 10(-6) mol/L, and the linear range comprises 2 decades, starting at the limit of quantification. To determine recovery rates, precision, and accuracy of the method, blank plasma samples were spiked with Gd-DTPA in three different concentrations. Blood plasma samples from 10 patients with normal renal function, having received Magnevist, were analyzed for Gd-DTPA and possible transmetalation products by CE/ESI-TOF-MS. The method was validated by determination of the total Gd concentration using inductively coupled plasma optical emission spectroscopy (ICP-OES). Transmetalation assays of Magnevist with and without supplementary iron were carried out in incubated whole blood samples.
为研究钆基造影剂钆喷酸葡胺（Gd-DTPA）的金属转移效应，开发了首个用于同时测定复杂临床样品中Gd-DTPA及其金属转移产物的分析方法。采用高效毛细管电泳（CE）分离Gd-DTPA、Fe-DTPA、Cu-DTPA、Zn-DTPA以及游离的二乙三胺五乙酸（DTPA）配体。CE与电喷雾电离飞行时间质谱（ESI-TOF-MS）联用，为分析血浆和全血等复杂样品提供了所需的灵敏度和出色的选择性。优化了分离和检测参数，并指出了CE/MS方法开发的关键步骤。检测限（LOD）为5×10⁻⁷mol/L，定量限（LOQ）为1.7×10⁻⁶mol/L，线性范围从定量限开始涵盖2个数量级。为确定该方法的回收率、精密度和准确度，向空白血浆样品中加入三种不同浓度的Gd-DTPA。采用CE/ESI-TOF-MS分析了10名接受过钆喷酸葡胺且肾功能正常的患者的血浆样品中的Gd-DTPA及可能的金属转移产物。通过电感耦合等离子体发射光谱法（ICP-OES）测定总钆浓度对该方法进行了验证。在孵育的全血样品中进行了有无补充铁的钆喷酸葡胺金属转移试验。
