title: Identification and quantification of potential metabolites of Gd-based contrast agents by electrochemistry/separations/mass spectrometry.
abstract: 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.
authors.affiliation: University of Münster, Institute of Inorganic and Analytical Chemistry, 48149 Münster, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Telgmann
authors.forename: Helene
authors.initials: H
authors.lastname: Faber
authors.forename: Sandra
authors.initials: S
authors.lastname: Jahn
authors.forename: Daniel
authors.initials: D
authors.lastname: Melles
authors.forename: Hannah
authors.initials: H
authors.lastname: Simon
authors.forename: Michael
authors.initials: M
authors.lastname: Sperling
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D055664:Electrochemical Techniques / Q000379:methods*; D005682:Gadolinium / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium