Analysis of whole blood samples with low gas flow inductively coupled plasma-optical emission spectrometry.

Low gas flow ICP-OES with a total argon consumption below 0.7 L/min is introduced for the analysis of trace elements in blood samples to investigate the influence of samples containing an organic solvent in a demanding matrix on the performance of this plasma for the first time. Therefore, gadolinium was determined in human plasma samples and mercury in red blood cells, human plasma, and precipitated plasma protein fraction. Limits of detection (LOD) were determined to be in the low microgram per liter range for the analytes and the accuracy of the method was assessed by comparison with a conventional Fassel-type torch-based ICP-OES. It was proven that the low gas flow ICP-OES leads to comparable results with the instrument based on the Fassel-type torch.

Speciation and isotope dilution analysis of gadolinium-based contrast agents in wastewater.

The fate of Gadolinium (Gd)-based contrast agents for magnetic resonance imaging (MRI) during sewage treatment was investigated. The total concentration of Gd in influent and effluent 2 and 24 h composite samples was determined by means of isotope dilution analysis. The balancing of Gd input and output of a sewage plant over seven days indicated that approximately 10% of the Gd is removed during treatment. Batch experiments simulating the aeration tank of a sewage treatment plant confirmed the Gd complex removal during activated sludge treatment. For speciation analysis of the Gd complexes in wastewater samples, high performance liquid chromatography (HPLC) was hyphenated to inductively coupled plasma sector field mass spectrometry (ICP-SFMS). Separation of the five predominantly used contrast agents was carried out on a new hydrophilic interaction liquid chromatography stationary phase in less than 15 min. A limit of detection (LOD) of 0.13 µg/L and a limit of quantification of 0.43 µg/L could be achieved for the Gd chelates without having to apply enrichment techniques. Speciation analysis of the 24 h composite samples revealed that 80% of the Gd complexes are present as Gd-BT-DO3A in the sampled treatment plant. The day-of-week dependent variation of the complex load followed the variation of the total Gd load, indicating a similar behavior. The analysis of sewage sludge did not prove the presence of anthropogenic Gd. However, in the effluent of the chamber filter press, which was used for sludge dewatering, two of the contrast agents and three other unknown Gd species were observed. This indicates that species transformation took place during anaerobic sludge treatment.

Speciation of Gd-based MRI contrast agents and potential products of transmetalation with iron ions or parenteral iron supplements.

The risk of transmetalation reactions between gadolinium complexes used as contrast agents for magnetic resonance imaging (MRI) and iron ions is examined under physiological conditions. A fast separation of gadopentetate (Gd-DTPA) and gadoterate (Gd-DOTA) and the respective Fe transmetalation products was accomplished by high-performance liquid chromatography. For detection, the LC system was coupled to an Orbitrap electrospray ionization mass spectrometer to achieve a detection limit as low as 50 nmol/L for Fe-DTPA. In vitro experiments revealed the formation of Fe-DTPA in blood plasma samples with Gd-DTPA and Fe(III) citrate. Analysis after different incubation times of the sample showed that the exchange of the metal ions is significantly dependent on time. If this reaction takes place in the body of MRI patients, this could explain why the disease nephrogenic systemic fibrosis (NSF) develops only after a longer retention of the linear Gd complex in the patient's body. Transmetalation either with endogenous Fe(II)/Fe(III) ions or with parenteral Fe supplements with Gd-DTPA could not be proven under the applied conditions. The high stability of Gd-DOTA is responsible that transmetalation between this macrocylic complex and neither of the Fe species was observed. These findings are important because NSF only develops after administration of Gd complexes with linear ligands. The results indicate that transmetalation reactions may be a trigger for the development of NSF, if free Fe(III) ions are accessible during a prolonged dwell time of Gd complexes with linear ligands in the patient's body.

Electrochemistry/liquid chromatography/mass spectrometry as a tool in metabolism studies.

Electrochemistry/liquid chromatography/mass spectrometry is a powerful complementary tool for the simulation of the oxidative metabolism of drugs and other xenobiotics.

Simple and rapid quantification of gadolinium in urine and blood plasma samples by means of total reflection X-ray fluorescence (TXRF).

A simple and rapid method to determine gadolinium (Gd) concentrations in urine and blood plasma samples by means of total reflection X-ray fluorescence (TXRF) was developed. With a limit of detection (LOD) of 100 µg L(-1) in urine and 80 µg L(-1) in blood plasma and a limit of quantification (LOQ) of 330 µg L(-1) in urine and 270 µg L(-1) in blood plasma, it allows analyzing urine samples taken from magnetic resonance imaging (MRI) patients during a period of up to 20 hours after the administration of Gd-based MRI contrast agents by means of TXRF. By parallel determination of the urinary creatinine concentration, it was possible to monitor the excretion kinetics of Gd from the patient's body. The Gd concentration in blood plasma samples, taken immediately after an MRI examination, could be determined after rapid and easy sample preparation by centrifugation. All measurements were validated with inductively coupled plasma mass spectrometry (ICP-MS). TXRF is considered to be an attractive alternative for fast and simple Gd analysis in human body fluids during daily routine in clinical laboratories.

Speciation analysis of gadolinium chelates in hospital effluents and wastewater treatment plant sewage by a novel HILIC/ICP-MS method.

The behavior of Gd chelates used in magnetic resonance imaging (MRI) within the process of sewage treatment is widely unknown. Due to the varying toxicity of the particular Gd species [J. M. Idee et al. Fundam. Clin. Pharmacol. 2006, 20, 563-576], it is important to not only investigate total Gd concentrations, but the Gd species as well. This work describes a novel method for speciation analysis of the most important gadolinium chelates in wastewaters. This novel approach consists of coupling hydrophilic interaction chromatography (HILIC) with inductively coupled plasma mass spectrometry (ICP-MS). HILIC/ICP-MS exhibits high separation efficiency for the simultaneous separation of the five predominantly applied MRI contrast agents and the required selectivity and sensitivity for trace determination in wastewater samples. For the first time, the distribution of particular Gd chelate complexes was determined in hospital effluent, municipal sewage, and wastewater treatment plant (WWTP) samples. The data were compared with the total concentration of Gd as determined by ICP-MS. The active compounds of Multihance, Dotarem, and Gadovist were identified in local WWTP samples. Interestingly, the macrocyclic, nonionic compound Gd-BT-DO3A (Gadovist) was found to be the most abundant Gd complex in all investigated samples. This is in contrast to prevalent assumptions that linear ionic Gd chelates such as Gd-DTPA (Magnevist) would be the predominant species [G. Morteani et al. Environ. Geochem. Health 2006, 28, 257-264 and M. Bau and P. Dulski, Earth Planet. Sci. Lett. 1996, 143, 245-255]. Although contrast agent concentrations tend to be reduced during wastewater treatment, Gd-BT-DO3A was still found in WWTP effluents.

Quantification and excretion kinetics of a magnetic resonance imaging contrast agent by capillary electrophoresis-mass spectrometry.

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.

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.

Speciation analysis of gadolinium-based MRI contrast agents in blood plasma by hydrophilic interaction chromatography/electrospray mass spectrometry.

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).

Quantitative analysis by microchip capillary electrophoresis: current limitations and problem-solving strategies.

Obstacles and possible solutions for the application of microchip capillary electrophoresis in quantitative analysis are described and critically discussed. Differences between the phenomena occurring during conventional capillary electrophoresis and microchip-based capillary electrophoresis are pointed out, with particular focus on electrolysis, bubble formation, clogging, surface interactions, injection and aspects related to the power supply. Current drawbacks are specified and improvements for successful quantitative microchip capillary electrophoresis are suggested.