Method Development for the Ultra Trace Speciation Analysis of Gadolinium

The development and application of highly sensitive methods for the speciation analysis of Gd have been presented within this thesis. Significant improvements of sensitivity could be achieved mostly by optimization of sample introduction for the HILIC/ICP-MS hyphenation. Thus, sufficient LODs were obtained for the direct analysis of drinking water samples. Additionally, complementary IC/ICP-MS and HILIC/ESI-MS methods were developed. New quantification strategies need to be part of future method development in the field of Gd speciation. Especially the application of isotope dilution analysis for HILIC/ICP-MS is likely to improve precision and accuracy of quantification results for environmental as well as for biological samples. Generally, two different approaches of this quantification strategy can be employed for speciation analysis: species-unspecific (online) isotope dilution and species-specific isotope dilution. In the first case, an isotopically enriched elemental Gd standard is continuously spiked into the HILIC flow behind the column. Thus, the online quantification of known and unknown species is possible. In contrast, the species-specific approach requires the synthesis of the individual complexes, incorporating isotopically enriched Gd, which is a more laborious approach.The analytical methods presented within this thesis allow further large-scale studies on the release of contrast agents into the environment and particularly on the effect of drinking water purification on the fate of Gd species. A time-dependent sampling strategy at particular steps in different waterworks can provide more detailed insight. In combination with further laboratory experiments regarding UV irradiation and ozonation, a more comprehensive evaluation of the stability of Gd species during drinking water purification should be possible. Regarding the structural elucidation of transformation products originating from UV irradiation, further investigations using ESI-MS are necessary. Moreover, the comparison with possible transformation products from ozonation should be considered. Further attempts have to be made to investigate the distribution of contrast agents in tissues from NSF patients and the formation of other Gd species. The combination of HILIC/ICP-MS for speciation analysis with quantitative elemental bioimaging by means of LA/ICP-MS should be applied for ongoing studies of samples from different patients. Furthermore, the analysis of different types of tissue from different organs can provide information on the distribution of Gd species in the whole organism. The latter approach would also require animal studies. Moreover, further efforts should be made to elucidate the structures of unidentified species in affected tissue. This will eventually lead to a better understanding of the pathogenesis of NSF.