Mild Dissolution/Recomplexation Strategy for Speciation Analysis of Gadolinium from MR Contrast Agents in Bone...

A species-dependent and total gadolinium quantification strategy for the analysis of bone and bone marrow samples was developed and applied to femurs of rats previously treated with different gadolinium-based contrast agents (GBCAs). A combined mild dissolution/recomplexation strategy allows the quantification of total Gd as well as the quantification of intact GBCA in bones within one analysis for the first time. Samples of rat bones and bone marrow were dissolved in low concentrations of hydrochloric acid and diethylenetriamine pentaacetate (DTPA). This is followed by the addition of excess In(III) to recomplex all free ligands, previously added DTPA as well as the ligands of GBCAs that were not stable during the dissolution step. Separation and quantification were carried out by means of high-performance liquid chromatography (HPLC) on a hydrophilic interaction liquid chromatography (HILIC) column with subsequent inductively coupled plasma-mass spectrometry (ICP-MS). The results show that the investigated GBCA with a macrocyclic ligand shows a higher tendency to stay intact in the bone tissues over time, while a GBCA with a linear ligand is decomplexed more rapidly four weeks after GBCA administration. Additionally, for all macrocyclic GBCAs, a similar limited gadolinium accumulation was observed in the bone and bone marrow. Whereas linear GBCAs showed a higher gadolinium accumulation, a difference was observed between bone and bone marrow, indicating a different biodistribution behavior.