A group of Japanese researchers have developed a HILIC separation of Gadolinium-based contrast agents using an aqueous mobile phase.
Background:Gadolinium chelates are used as contrast agents for medical magnetic resonance imaging (MRI) since the 80's because of the excellent magnetic properties of gadolinium. About 20,000,000 patients per year are investigated by this diagnostic tool, each one receiving typically around 1.2 g of gadolinium. Most of the Gd is excreted by the patients within the first day after application with urine entering the environment via waste water. In recent decades, the amount of Gd in river water has been increasing owing to the input of Gd-based contrast agents. Since Gd-based contrast agents are very stable complexes, they are excreted in unmetabolized form and are suspected not to be biodegradable in the aquatic environment. In order to study the fate of these compounds within waste water treatment plants, Gd speciation analysis at ultratrace levels is required. To identify and quantify the Gd-based contrast agents in water samples, researchers from the University of Münster had developed in 2009 the technique of hydrophilic interaction liquid chromatography (HILIC) hyphenated with inductively coupled plasma-mass spectrometry (ICP-MS) (see the EVISA News below). The mobile phase for eluting the different Gd-complexes from the HILIC column at that time was acetonitrile, calling for the addition of oxygen to the plasma gas for avoiding carbon build-up on the cones and also requiring a robust rf generator, tolerating the solvent load.
Figure 1: Structures of some frequently applied gadolinium-based
contrast agents for MRI examinations with respective trademarks
The new study:
To avoid the drawbacks coming with the introduction of organic solvents into the plasma, the researchers from Japan developed a method using a mobile phase consisting of an ammonium acetate buffer diluted with pure water. Despite the absence of an organic solvent in the mobile phase, six Gd-based contrast agents, Gd-DTPA, Gd-EOB-DTPA, Gd-DOTA, Gd-DTPA-BMA, Gd-BT-DO3A, and Gd-HP-DO3A, were successfully separated during an isocratic elution lasting 13 min. Obtained detection limits were in the range of 3.4 - 22 ng/L, depending on the Gd-complex, and only a factor of 1.5 - 5 worse in comparison to the best detection limits reported for HILIC separation using organic solvent as eluent (see Birka et al. 2016). Such detection power allowed the analysis of river water samples near the outfall of a wastewater treatment plant. Three GBCAs were found in the water samples, namely Gd-DOTA, Gd-BT-DO3A, and Gd-HP-DO3A, indicating that at least some of the Gd-based contrast agents are passed through treatment in a WWTP. In addition to Gd-based contrast agents, unidentified Gd compounds were found to be present in river water. These results infer that transformation and/or dissociation of Gd chelates may be caused during the treatment procedure in a WWTP.
The Original study
Satoki Okabayashi, Leona Kawane, Nanda Yusentri Mrabawani, Takahiro Iwai, Tomohiro Narukawa, Motohiro Tsuboi, Koichi Chiba,
Speciation analysis of Gadolinium-based contrast agents using aqueous eluent-hydrophilic interaction liquid chromatography hyphenated with inductively coupled plasma-mass spectrometry, Talanta, 222 (2021) 121531.
DOI: 10.1016/j.talanta.2020.121531
Used techniques and instrumentation:
Agilent Technologies Inc. - 7700x ICP-MS Shimadzu Europe - LC 20AD Related studies (newest first)
U. Lindner, J. Lingott, S. Richter, W. Jiang,
N. Jakubowski, U. Panne,
Analysis of Gadolinium-based contrast agents in tap water with a new
hydrophilic interaction chromatography (ZIC-cHILIC) hyphenated with
inductively coupled plasma mass spectrometry, Anal. Bioanal. Chem., 407
(2015) 2415–2422.
DOI: 10.1007/s00216-014-8368-5 M. Birka, C.A. Wehe,
L. Telgmann,
M. Sperling, U. Karst,
Sensitive
quantification of gadolinium-based magnetic resonance imaging contrast
agents in surface waters using hydrophilic interaction liquid
chromatography and inductively coupled plasma sector field mass
spectrometry, J. Chromatogr. A, 1308 (2013) 125–131.
DOI: 10.1016/j.chroma.2013.08.017 U. Lindner, J. Lingott, S. Richter,
N. Jakubowski, U. Panne, Speciation
of gadolinium in surface water samples and plants by hydrophilic
interaction chromatography hyphenated with inductively coupled plasma
mass spectrometry, Anal. Bioanal. Chem. 405 (2013) 1865–1873.
DOI: 10.1007/s00216-012-6643-x
L.
Telgmann, C.A. Wehe, M. Birka, J. Künnemeyer, S. Nowak,
M. Sperling,
U.
Karst,
Speciation and isotope dilution analysis of gadolinium-based
contrast agents in wastewater, Environ. Sci. Technol., 46 (2012)
11929–11936.
DOI: 10.1021/es301981z C.S.K. Raju, A. Cossmer, H. Scharf, U. Panne, D. Lück,
Speciation of gadolinium based MRI contrast agents in environmental
water samples using hydrophilic interaction chromatography hyphenated
with inductively coupled plasma mass spectrometry, J. Anal. At.
Spectrom., 25 (2010) 55–61.
DOI: 10.1039/b919959d J. Künnemeyer, L. Terborg,
B. Meermann, C. Brauckmann, I. Möller, A. Scheffer,
U. Karst,
Speciation analysis of gadolinium chelates in hospital effluents and wastewater treatment plant sewage by a novel HILIC/ICP-MS method, Environ. Sci. Technol., 43 (2009) 2884–2890.
DOI: 10.1021/es803278n
Brief summary: Speciation analysis for the study of metallodrugs and their biomolecular interactions
Related EVISA News (Newest first) March 14, 2016: Tracing Gadolinium-based Contrast Agents from Wastewater, via Surface Water to Drinking Water
March 4, 2015: Detection of Gd-based contrast agent in the skin of a patient eight years after administration October 29, 2012: Identification and quantification of potential metabolites of Gd-based contrast agents October 18, 2012: The behavior of Gd-based contrast agents during wastewater treatment September 15, 2010: US FDA Announces Gadolinium-Based MRI Contrast Agent Warning March 25, 2010: Publication on the separation of Gd-based contrast agents awarded May 4, 2009: Gadolinium speciation analysis in search for the cause of nephrogenic systemic fibrosis (NSF) April 14, 2009: Gadolinium-based MRI contrast agents found intact in the outlet of a waste water treatment plantlast time modified: December 2, 2020
