Vitamin D deficiency is present in a majority of haemodialysis patients. Supplementation with cholecalciferol is safe, well tolerated and reasonable to replenish vitamin D stores in haemodialysis patients. However, only 57% of patients achieved recommended calcidiol levels, thus favouring additional dose-finding studies.

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).

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.

A novel method for the analysis of Gadolinium-based contrast agents in complex clinical matrices is presented. Three commonly applied ionic contrast agents for magnetic resonance imaging were separated by CE and detected by ESI-MS. Blank urine samples were spiked with Dotarem (Gd-DOTA, Gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), Magnevist (Gd-DTPA, Gadolinium-diethylenetriaminepentaacetic acid) and Multihance (Gd-BOPTA, Gadolinium-benzyloxymethyl-diethylenetriaminepentaacetic acid) to determine the recovery rates. The figures of merit were determined with LODs as low as 2.0 x 10(-7) mol/L for Gd-DOTA, 5.0 x 10(-7) mol/L for Gd-DTPA and 1.0 x 10(-6) mol/L for Gd-BOPTA. The respective LOQs were 6.6 x 10(-7) mol/L for Gd-DOTA, 1.5 x 10(-6) mol/L for Gd-DTPA and 3.3 x 10(-6) mol/L for Gd-BOPTA. The linear working range comprised two orders of magnitude starting at the LOQ, with regression coefficients of R > or = 0.999 for all investigated analytes. Using this CE-MS method, Gd-DOTA was quantified in seven urine samples obtained at different times after delivery from a volunteer magnetic resonance imaging patient who was treated with Dotarem. Additionally, total Gd concentrations were determined by means of ICP-optical emission spectroscopy to validate the CE-MS data. To compensate for dietary dilution effects of the urine samples, creatinine was determined by HPLC with UV/Vis absorption detection. Gd-DOTA concentrations were normalized to urinary creatinine, illustrating the fast excretion kinetics of Gd-DOTA.