Iodinated X-ray Contrast Agents Research Articles

Iodine speciation using thin-layer chromatography coupled to inductively coupled plasma-mass spectrometry by means of an extraction device

Thin-layer chromatography (TLC) has been coupled to inductively coupled plasma-mass spectrometry (ICP-MS) using an extraction device, which allows a nearly complete recovery of compounds from thin-layer chromatograms within short extraction times, small volumes and without contamination. Iodinated X-ray contrast agents were separated and analyzed with the newly developed setup. Iodine speciation analysis was carried out with deviations between the expected and the measured concentrations in spiked urine samples from 3.2 to 16.6%.

Contrast Dose-to-Creatinine Clearance Ratio as a Potential Indicator of Risk for Radiocontrast-Induced Nephropathy

Identification of risk factors is important for preventing radiocontrast-induced nephropathy (RCIN). Contrast dose and renal function have been shown in most but not all studies to be risk factors for RCIN. We are investigating the ratio of contrast dose to creatinine clearance (D/CrCL) as a risk indicator. Theory shows that the D/CrCL ratio equals the area under the concentration-time curve (AUC), an accepted measure of systemic exposure. This study investigated the correlation between calculated D/CrCL and experimentally measured AUC for the contrast agent iodixanol. Experimental data on AUC from a phase 1 study of iodixanol were plotted against the D/CrCL ratio and the degree of correlation was determined. Experimentally determined AUC data correlate highly with the D/CrCL ratio. The D/CrCL ratio is a rapid and accurate way to estimate AUC for an iodinated x-ray contrast agent without the need for multiple blood samples.

Microdamage in bone: Surface analysis and radiological detection

Microdamage accumulation leads to reduced bone strength and fracture. Intact, damaged and Rose Bengal stained cortical bone specimens were studied using SEM and EDXA imaging. SEM coupled with EDXA studies showed selective labelling of surface damage due to binding of dye at free lattice sites. A series of novel iodinated X-ray contrast agent were synthesised. These agents demonstrated excellent stability, water solubility and lack of atropisomerism. Preliminary imaging studies, using cone-beam μ-CT, demonstrated their ability to provide visible contrast in the solid state on bone surfaces.

Analysis of iodinated X-ray contrast agents in water samples by ion chromatography and inductively-coupled plasma mass spectrometry

In this paper, an analytical method for the determination of six iodinated X-ray contrast agents (amidotrizoic acid, iohexol, iomeprol, iopamidol, iopromide, and ioxitalamic acid), iodide, and iodate in water samples is presented. The method is based on a separation of the analytes by ion chromatography (IC) and a subsequent detection by inductively-coupled plasma mass spectrometry (ICP-MS). The method was optimised with respect to separation conditions (column type and eluent composition) and extensively validated. Without pre-concentration of the samples, limits of detection below 0.2 μg/l could be achieved whereby reproducibility was below 6% for all compounds under investigation.

Reorientational dynamics, hydrogen bonding and hydrophilicity of X-ray contrast agents in solution

In order to probe the hydrophilic and lipophilic properties of iodinated X-ray contrast agents, a new parameter was introduced, the relative reduced molecular correlation time of reorientational motion. Therefore, the viscosities and 13C spin–lattice relaxation times of the five contrast agents iopromide, iohexol, iopamidol, iotetrol and N-acetyliotetrol in their solutions with dimethylsulfoxide, water and methanol were measured. From these data the relative reduced molecular correlation times were evaluated, and a relation between these correlation times and measured water/butanol partition coefficients [log(P) values] could be established. The order for the relative reduced molecular correlation times is: iopromide > iopamidol > iohexol > N-acetyliotetrol > iotetrol. When subdividing the contrast agents into classes of structurally similar compounds, the same order was observed for the log(P) values, namely iopromide > iopamidol > iohexol. Copyright © 2001 John Wiley & Sons, Ltd.

Environmental Risk Assessment for the Widely Used Iodinated X-Ray Contrast Agent Iopromide (Ultravist)

Iodinated X-ray contrast media are diagnostic pharmaceuticals that are applied to enhance the contrast between organs or vessels examined and surrounding tissues during radiography. These substances are applied in doses up to ca. 200 g per person (corresponding to approx 100 g iodine) and are rapidly excreted. In the sewage system they contribute to the burden of adsorbable organic halogens (AOX). To assess the potential environmental impact of this release, studies on environmental fate and effects were conducted for a risk assessment of the frequently used X-ray contrast medium iopromide (brand name: Ultravist). A screening test for biological degradation (OECD Screening Test 301 E) led to iopromide being classified as not readily biodegradable. Therefore, the predicted environmental concentration (PEC) in surface water was calculated in a first step. The resulting concentration of 2 μg/liter was then compared in a second step with the predicted no-effect concentration as derived from a battery of ecotoxicity tests. In short-term toxicity tests with bacteria (Vibrio fisheri,Pseudomonas putida), algae (Scenedesmus subspicatus), crustaceans (Daphnia magna), and fish (Danio rerio,Leuciscus idus) no toxic effects were detected at the highest tested concentration of 10 g/liter. In a chronic toxicity test withD. magnano effect was observed at the highest tested concentration of 1 g/liter. Using an assessment factor of 100 the ratio between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC) was calculated to be ≤0.0002. This low value indicates that no environmental risk has to be expected as a result of the release of iopromide into the aquatic environment.

Optimisation of the Preparation and Isolation of 5-Amino-2,4,6-triiodoisophthalic Acid Dichloride

A scaleable process for the chlorination of 5-amino-2,4,6-triiodoisophthalic acid to the corresponding acid chloride, a building block for the synthesis of iodinated X-ray contrast agents, has been developed. Two dimeric byproducts have been isolated and assigned structures consistent with an amide and an anhydride. Hydrolysis of the N-sulfinyl intermediate and simultaneous crystallisation of the phthalic acid chloride have been optimised by applying fractional factorial design.

Sterile Filtration of NanoCrystal™ Drug Formulations

A Nano Crystal™ dispersion of the iodinated x-ray contrast agent iodipamide was prepared by wet milling the drug substance in the presence of Pluronic® F127 stabilizer. The mean particle size of the formulation was 98 nm and all drug particles in the formulation were smaller than 220 nm as determined by dynamic light scattering. Approximately 1 liter of dispersion was filtered through a sterile 0.2-μm disposable capsule filter (Supor® 200 DCF™, 0.I m2 effective filtration area [EFA], Gelman Sciences) to condition the capsule. No drug concentration or size distribution changes were detected after the filtration process. The microbiological validation tests were performed using Pseudomonas diminuta organisms to challenge the capsule under simulated worst-case process conditions. The results showed that the Supor 200 DCF was able to retain 100% Pseudomonas diminuta organisms (≥107 organisms per cm2 of effective filtration area). Thus, this study demonstrated that terminal filtration is a feasible process to sterilize Nano Crystal™ drug dispersions that may be chemically or physically unstable at elevated temperatures and thus not amenable to terminal heat sterilization.

The non-ionic isotonic contrast agents. Perspectives and controversies.

The non-ionic isotonic contrast agents represent a new class of intravascular iodinated x-ray contrast agents. They are highly hydrophilic, resulting in low chemotoxicity, are non-ionic, thereby eliminating Coulomb interactions, and are formulated in solutions iso-osmolar with the respective body fluids. Invitro testing, organ specific toxicity studies and overall systemic toxicity assessments such as LD50 measurements all point to an excellent toxicity profile. This justify their application in high dose procedures where their low toxicity may be distinctly advantageous. Their iso-osmolality, possibly combined with a slower diffusion of the larger molecules across vessel walls and out of the vascular space, may play a significant role in producing better quality venous phase images following arteriography and arterial phase images following venous injection. This may have implications for the quality of IV-DSA, the venous phase of arteriograms, CT-portography and spiral CT arteriography.

Clinical safety of iotrolan 280: the Japanese experience

Iortrolan is a new non ionic, dimeric, iodinated X-ray contrast agent that is isotonic with body fluids. In Japan iotrolan (280 mg iodin/ml) was evaluated in well controlled multi-center trials to compare its efficacy, safety and utility with that of iopamidol (300 mg iodine/ml), considered to be the standard non-ionic monomeric X-ray contrast agent in this country. Safety data from four phase III studies are presented. Two studies involved intra-arterial injection (cerebral and peripheral arteriography) and two were intravenous (computed tomography and urography). Iotrolan 280 was administered to 333 patients and 337 patients received iopamidol 300. The safety evaluation of iotrolan 280 was by assessment of adverse events, pain and heat sensation following intra-arterial injection, as well as clinical laboratory tests and an overall safety rating by the investigator. The results showed that there was a significant reduction in pain and heat sensation with iotrolan 280. Fewer adverse events were seen with iotrolan 280 compared with iopamidol 300, but this difference was not signicant in this limited patient population. Clinical laboratory tests showed no clinically relevant change attributed to contrast agent injection not any significant difference between the two agents. The overall safety rating, based on all of the above results, was “safe” in 94.6% of patients receiving iotrolan 280 and 92.0% of patients receiving iopamidol 300, suggesting that iotrolan 280 was at least as safe for intra-arterial and intravenous use as iopamidol 300.

5242683 Contrast media comprising a paramagnetic agent and an iodinated agent for X-ray and MRI

There is provided a contrast medium comprising a physiologically tolerable paramagnetic metal species containing substance together with a water soluble iodinated X-ray contrast agent. The contrast medium can be used for both X-ray and magnetic resonance imaging of the gastro-intestinal tract but overcomes or greatly reduces the side effects experienced by mannitol-containing prior art contrast media.

Polarographic behavior of iodinated X-ray contrast agents in buffered media.

Polarographic behavior of iodinated X-ray contrast agents in buffered media.

Polarographic Behavior of Iodinated X-Ray Contrast Agents Jn Buffered Media

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolarographic Behavior of Iodinated X-Ray Contrast Agents Jn Buffered MediaPeter. Kabasakalian and James. McGIottenCite this: Anal. Chem. 1959, 31, 4, 513–516Publication Date (Print):April 1, 1959Publication History Published online1 May 2002Published inissue 1 April 1959https://doi.org/10.1021/ac50164a017RIGHTS & PERMISSIONSArticle Views12Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (513 KB) Get e-Alerts Get e-Alerts