Health & Environmental Research Online (HERO)


Print Feedback Export to File
1870895 
Journal Article 
Identification and quantification of potential metabolites of Gd-based contrast agents by electrochemistry/separations/mass spectrometry 
Telgmann, L; Faber, H; Jahn, S; Melles, D; Simon, H; Sperling, M; Karst, Uwe 
2012 
Yes 
Journal of Chromatography A
ISSN: 0021-9673
EISSN: 1873-3778 
1240 
147-155 
English 
22525874 
WOS:000304491700017 
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. 
Gadolinium; Contrast agent; MRI; NSF; Gd-DTPA; Electrochemistry; Drug metabolism; CE/ESI-MS; CE/ICP-MS; LC/ESI-MS; LC/ICP-MS