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通过毛细管电泳-质谱联用技术对磁共振成像造影剂进行定量分析及排泄动力学研究

Quantification and excretion kinetics of a magnetic resonance imaging contrast agent by capillary electrophoresis-mass spectrometry.

作者信息

Künnemeyer Jens, Terborg Lydia, Nowak Sascha, Brauckmann Christine, Telgmann Lena, Albert Anastasia, Tokmak Faruk, Krämer Bernhard K, Günsel Andreas, Wiesmüller Gerhard A, Karst Uwe

机构信息

University of Münster, Institute of Inorganic and Analytical Chemistry, Münster, Germany.

出版信息

Electrophoresis. 2009 May;30(10):1766-73. doi: 10.1002/elps.200800831.

Abstract

A novel method for the analysis of Gadolinium-based contrast agents in complex clinical matrices is presented. Three commonly applied ionic contrast agents for magnetic resonance imaging were separated by CE and detected by ESI-MS. Blank urine samples were spiked with Dotarem (Gd-DOTA, Gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), Magnevist (Gd-DTPA, Gadolinium-diethylenetriaminepentaacetic acid) and Multihance (Gd-BOPTA, Gadolinium-benzyloxymethyl-diethylenetriaminepentaacetic acid) to determine the recovery rates. The figures of merit were determined with LODs as low as 2.0 x 10(-7) mol/L for Gd-DOTA, 5.0 x 10(-7) mol/L for Gd-DTPA and 1.0 x 10(-6) mol/L for Gd-BOPTA. The respective LOQs were 6.6 x 10(-7) mol/L for Gd-DOTA, 1.5 x 10(-6) mol/L for Gd-DTPA and 3.3 x 10(-6) mol/L for Gd-BOPTA. The linear working range comprised two orders of magnitude starting at the LOQ, with regression coefficients of R > or = 0.999 for all investigated analytes. Using this CE-MS method, Gd-DOTA was quantified in seven urine samples obtained at different times after delivery from a volunteer magnetic resonance imaging patient who was treated with Dotarem. Additionally, total Gd concentrations were determined by means of ICP-optical emission spectroscopy to validate the CE-MS data. To compensate for dietary dilution effects of the urine samples, creatinine was determined by HPLC with UV/Vis absorption detection. Gd-DOTA concentrations were normalized to urinary creatinine, illustrating the fast excretion kinetics of Gd-DOTA.

摘要

本文提出了一种用于分析复杂临床基质中钆基造影剂的新方法。通过毛细管电泳(CE)分离并采用电喷雾电离质谱(ESI-MS)检测三种常用于磁共振成像的离子型造影剂。在空白尿液样本中加入多它灵(钆-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸,Gd-DOTA)、马根维显(钆-二乙三胺五乙酸,Gd-DTPA)和多安吉(钆-苄氧甲基-二乙三胺五乙酸,Gd-BOPTA)以测定回收率。测定的品质因数显示,Gd-DOTA的检测限低至2.0×10⁻⁷mol/L,Gd-DTPA为5.0×10⁻⁷mol/L,Gd-BOPTA为1.0×10⁻⁶mol/L。各自的定量限分别为:Gd-DOTA为6.6×10⁻⁷mol/L,Gd-DTPA为1.5×10⁻⁶mol/L,Gd-BOPTA为3.3×10⁻⁶mol/L。线性工作范围从定量限开始涵盖两个数量级,所有研究分析物的回归系数R≥0.999。使用这种CE-MS方法,对一名接受多它灵治疗的磁共振成像志愿者患者产后不同时间采集的7份尿液样本中的Gd-DOTA进行了定量。此外,通过电感耦合等离子体发射光谱法(ICP-OES)测定总钆浓度以验证CE-MS数据。为补偿尿液样本的饮食稀释效应,采用高效液相色谱-紫外/可见吸收检测法测定肌酐。将Gd-DOTA浓度标准化为尿肌酐浓度,说明了Gd-DOTA快速的排泄动力学。

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