Determination of gadolinium-based MRI contrast agents in fresh and oceanic waters of Australia
Researchers from the University of Technology Sydney and from University of Münster have developed a method employing micro-solid phase extraction followed by HILIC-ICP-MS for the determination of the most often used gadolinium-based contrast agents in the aquatic environment of Australia.
A variety of gadolinium complexes are used as contrast agents to improve diagnostic capabilities of magnetic resonance imaging (MRI). The most often administered chelates are depicted in Fig. 1.
Figure 1: Structures of the frequently applied gadolinium-based contrast agents for MRI examinations with respective trademarks
On a global scale, more than 30 million examinations per year are performed with the aid of such gadolinium-based contrast agents (GBCAs). After their intravenous injection, the contrast agents are rapidly and mostly unmetabolized excreted via the urine and enter unaltered the aquatic environment via effluents of local waste-water treatment plants. The relatively high amount of approx. 1 g of gadolinium per administration and the frequent use of GBCAs results in a substantial discharge of gadolinium into the environment around medical centers, causing anthropogenic Gd anomalies in the natural distribution of rare earth elements. Such anomalies have been reported for surface waters around the globe and GBCAs could be traced even in the drinking water originating from such aquatic resources (EVISA has frequently reported about such studies, see the related news below). While methodology has been improved over recent years, allowing the determination of GBCAs at trace levels found in drinking water, methods for speciation analysis in complex matrices like seawater have not been reported so far.
The new study:
Now a group of researchers from Australia and Germany aimed at the development of a method for the gadolinium speciation analysis of seawater. Such method not only calls for very low detection limits but also for the elimination of the complex seawater matrix. The researchers achieved these goals by combination of preconcentration via micro-solid phase extraction (µSPE) and separation of Gd-species by hydrophilic interaction liquid chromatography (HILIC). The detection by quadrupole-based inductively coupled plasma mass spectrometry (ICP-MS) was specially tuned for improved ion transmission by modifying ion extraction, transport and increasing the mass bandwidth of the quadrupole.
For the preconcentration of GBCAS from seawater, an automated µSPE method was developed making use of µCARB extraction cartridges. Sample volumes between 250 and 1000 µL were loaded onto the sorbent material and eluted with 250 µL of 73% acetonitrile. Chromatographic separations of the GBCAs were performed using an Accucore HILIC silica column with isocratic elution using ammonium acetate buffer at a pH of 5.3 and 80% acetonitrile. Under optimized conditions with column temperature set to 40°C, and a relatively high flow rate of 1.1. ml/min, separation was achieved in less than three minutes.
Detection of the Gd-species was performed by using a 7700 series ICP-MS system (Agilent Technologies). To improve the detection of Gd at 156 amu, the system was used with an increased mass bandpass mode. The parameters of the bandpass mode consisting of a DC voltage and a RF voltage applied to the four rods of the quadrupole were optimized for best signal to noise ratios of Gd (see figure 2).
The bandpass mode is decreasing mass resolution allowing for transmission of several isotopes simultaneously (see figure 3). The increased ion transmission of the bandpass mode increases sensitivity for Gd by a factor of 44 compared against the standard mode for monitoring the most abundant Gd isotope (158Gd, 24.84%). To prevent potential polyatomic interferences and to reduce background noise, He and H2 were used as cell gases.
A standard mix containing four GBCAs at a level of 100 ng/L were analysed by HILIC-ICP-MS employing a standard mode and the bandpass mode, respectively. Figure 4 shows the appropriate separation of all four species in less than three minutes. The detection limits for all four species were between 18 and 24 ng/L in the bandpass mode, about a factor of 5 better than the standard mode. Using this method, Gd-DOTA and Gd-BT-DO3A were detected in coastal seawater within the proximity of a wastewater effluent.
The Original study
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