Analysis of the contrast agent Magnevist and its transmetalation products in blood plasma by capillary electrophoresis/electrospray ionization time-of-flight mass spectrometry.

To study transmetalation effects of the gadolinium-based contrast agent Magnevist (Gd-DTPA), the first analytical method for the simultaneous determination of Gd-DTPA and its transmetalation products in complex clinical samples was developed. The high separation efficiency of capillary electrophoresis (CE) was employed to separate Gd-DTPA, Fe-DTPA, Cu-DTPA, Zn-DTPA, and the free DTPA (diethylenetriaminepentaacetic acid) ligand. The coupling of CE with electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) provided the required sensitivity and excellent selectivity for the analysis of complex samples, such as blood plasma and whole blood. Separation and detection parameters were optimized, and crucial steps for CE/MS method development are pointed out. Limit of detection (LOD) is 5 x 10(-7) mol/L, limit of quantification (LOQ) is 1.7 x 10(-6) mol/L, and the linear range comprises 2 decades, starting at the limit of quantification. To determine recovery rates, precision, and accuracy of the method, blank plasma samples were spiked with Gd-DTPA in three different concentrations. Blood plasma samples from 10 patients with normal renal function, having received Magnevist, were analyzed for Gd-DTPA and possible transmetalation products by CE/ESI-TOF-MS. The method was validated by determination of the total Gd concentration using inductively coupled plasma optical emission spectroscopy (ICP-OES). Transmetalation assays of Magnevist with and without supplementary iron were carried out in incubated whole blood samples.

Formulation considerations of gadolinium lipid nanoemulsion for intravenous delivery to tumors in neutron-capture therapy.

The effects of the formulation and particle composition of gadolinium (Gd)-containing lipid nanoemulsion (Gd-nanoLE) on the biodistribution of Gd after its intravenous (IV) injection in D(1)-179 melanoma-bearing hamsters were evaluated for its application in cancer neutron-capture therapy. Gd-nanoLEs whose particles had an oily core (soybean oil, ethyl oleate, lipiodol, or triolein) and a surface layer of hydrogenated phosphatidylcholine, gadolinium-diethyl-enetriaminepentaacetic acid-distearylamide, and a cosurfactant (Myrj 53, Brij 700, or HCO-60) were prepared by a thin-layer hydration-sonication method. Biodistribution data revealed that Brij 700 and HCO-60 prolonged the retention of Gd in the blood and enhanced its accumulation in tumors. Among the core components employed, soybean oil yielded the highest Gd concentration in the blood and tumor and the lowest in the liver and spleen. Gd-nanoLEs with a Gd content of 1.5-4.5 mg/ml could be formulated by using HCO-60 and soybean oil at a constant oil-to-water ratio, and by enriching Gd in the surface layer with the particle size maintained below 100 nm. When each Gd-nanoLE was IV injected once or twice at a 24-h interval, the Gd concentration in the tumor correlated well with the total dose of Gd, and it reached a maximum of 189 microg/g wet tumor. This maximum Gd level was greater than the limit required for significantly suppressing tumor growth in neutron-capture therapy.