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The use of gadolinium-based contrast agents (GBCA) is integral to the field of diagnostic magnetic resonance imaging (MRI). Pharmacokinetic evaluation of the plasma clearance of GBCA is required for all new agents or improved formulations, to address concerns over toxicity or unforeseen side effects. Current methods to measure GBCA in plasma lack either a rapid readout or the sensitivity to measure small samples or require extensive processing of plasma, all obstacles in the development and characterization of new GBCA. Here, we quantify the plasma concentration of a labeled analogue of a common clinical GBCA by ligand triplet harvesting and energy transfer. The nonemittive GBCA becomes a "dark donor" to a fluorescent detector molecule, with a lower limit of detection of 10(-7) M in unprocessed plasma. On a time scale of minutes, we determine the plasma clearance rate in the wild-type mouse, using time-resolved fluorescence on a standard laboratory plate reader.

The first analytical method for simultaneous speciation analysis of five of the most important gadolinium-based magnetic resonance imaging (MRI) contrast agents in blood plasma samples was developed. Gd-DTPA (Magnevist), Gd-BT-DO3A (Gadovist), Gd-DOTA (Dotarem), Gd-DTPA-BMA (Omniscan), and Gd-BOPTA (Multihance) were separated by hydrophilic interaction liquid chromatography (HILIC) and detected with electrospray mass spectrometry (ESI-MS). Spiking experiments of blank plasma with Magnevist and Gadovist were performed to determine the analytical figures of merit and the recovery rates. The limits of detection ranged from 1 x 10 (-7) to 1 x 10 (-6) mol/L depending on the ionization properties of the individual compounds, and limits of quantification ranged from 5 x 10 (-7) to 5 x 10 (-6) mol/L. The linear concentration range comprised 2 orders of magnitude. With application of this method, blood plasma samples of 10 healthy volunteers, with Magnevist or Gadovist medication, were analyzed for Gd-DTPA and Gd-BT-DO3A, respectively. The obtained results were successfully validated with inductively coupled plasma-optical emission spectroscopy (ICP-OES).