Advanced methodological framework for speciation analysis of gadolinium in skin tissue following MRI contrast agent exposure

A method for quantitative speciation analysis of residual gadolinium in skin following gadolinium-based contrast agent exposure was developed for the first time. Polyethersulfone was identified as a suitable filter material for these compounds, allowing complete recovery of spiked contrast agents. In contrast, decreasing recoveries with increasing charge of the compound were observed for regenerated cellulose and cellulose triacetate as filter materials. The developed method entailed the utilization of bead beating for tissue homogenization, and the release of yttrium from ceramic beads was shown to result in the gadolinium transmetalation of a linear gadolinium-based contrast agent. A three-step centrifugation of homogenized skin samples, followed by filtration, was performed to extract hydrophilic species for analysis. In combination with using the respective europium chelates as internal standards, this approach enabled the complete recovery of macrocyclic contrast agents from spiked tissue. Quantitative speciation analysis of the biological extracts was conducted by means of anion exchange chromatography hyphenated to inductively coupled plasma-mass spectrometry. This analytical strategy applied to rat skin tissue after repeated administration of macrocyclic contrast agents showed that about a quarter of the residual gadolinium in skin tissue was present in the aqueous extract one month after the last injection. The majority of this water-soluble gadolinium was confirmed by speciation analysis to be the intact administered contrast agent. The presented methodological framework can serve as a first step towards exhaustive speciation analysis of residual gadolinium in skin matrix.