Efficient degradation and deiodination of iopamidol by UV/sulfite process: Assessment of typical process parameters and transformation paths.

Iopamidol (IPM) is widely used in medical clinical examination and treatment and has immeasurable harm to the ecological environment. The combination of UV and sulfite (UV/sulfite) process was developed to degrade IPM in this study. In contrast to that almost no removal of IPM was observed under sulfite reduction alone, the UV/sulfite process could efficiently reductively degrade IPM with the observed rate constant (kobs) of 2.08 min-1, which was nearly 4 times that of UV irradiation alone. The major active species in the UV/sulfite process were identified as hydrated electrons (eaq-) by employing active species scavengers. The influence of the initial pH, sulfite dosage, IPM concentration, UV intensity and common water matrix were evaluated. The degradation of IPM reached nearly 100% within only 2.5 min at pH 9, and kobs increased at higher initial sulfite dosages and greater UV intensities. HCO3- had a limited effect on the degradation of IPM, while humic acid (HA) was found to be a strong inhibitor in the UV/sulfite process. With the synergistic action of UV/sulfite, most of the iodine in IPM was found to release in the form of iodide ions (up to approximately 98%), and a few formed iodide-containing organic compounds, reducing significantly the toxicity of degradation products. Under direct UV irradiation and free radical reduction (mainly eaq-), 15 transformation intermediates of IPM were produced by amide hydrolysis, deiodination, hydroxyl radical addition and hydrogen abstraction reactions, in which free radical attack accounted for the main part. Consequently, the UV/sulfite process has a strong potential for IPM degradation in aquatic environments.

How we do it: shifting MR arthrogram compounding from the fluoroscopy suite to the sterile pharmacy.

OBJECTIVE: To assess the impact of shifting arthrogram injectate compounding from the fluoroscopy suite to the main hospital sterile pharmacy on cost, examination delays, and infection rates. MATERIALS AND METHODS: All arthrograms from the 12 months before (629 in total) and the 12 months after (699 in total) the change in arthrogram preparation procedure were compared to identify differences in examination delays and infection rate. The arthrogram formulation was sent to the Compounder's International Analytical Laboratory for stability testing. Finally, cost per injection analysis was performed to compare fluoroscopy suite with sterile pharmacy compounding. RESULTS: In the 699 arthrograms performed in the 12 months following transfer of arthrogram preparation to the main hospital pharmacy, there were 0 reported examination delays, 0 reported infections, and a 53% decrease in the material cost per arthrogram. There were three recorded instances of fluoroscopy suite preparation of arthrogram injectate due to unexpected add-on patients. Outside stability testing determined that the arthrogram injectate retained at least 90% potency 30 h post-preparation. CONCLUSION: Shifting the compounding of the arthrogram injectate from the fluoroscopy room to the main hospital sterile pharmacy provides a modest cost saving and can be accomplished without examination delays or any increase in infection rate. It brought our practice into compliance with USP797, which is the current guideline for compounding practitioners, by transferring the compounding preparation of the arthrogram injectate from a procedure room to the sterile pharmacy.

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents.

OBJECTIVES: The aim of this study was to evaluate 4 nonionic x-ray iodinated contrast agents (CAs), commonly used in radiographic procedures, as novel chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) agents by assessing their in vitro exchange properties and preliminary in vivo use as tumor enhancing agents. MATERIALS AND METHODS: The CEST properties, as function of pH (range, 5.5-7.9) and of radio frequency conditions (irradiation field strength range of 1-9 µT and time of 1-9 seconds), have been determined at 7 T and 310 K for 4 x-ray CAs commonly used in clinical settings, namely, iomeprol, iohexol, ioversol, and iodixanol. Their in vivo properties have been investigated upon intravenous injection in a murine HER2+ breast tumor model (n = 4 mice for each CA) using both computed tomography (CT) and MRI modalities. RESULTS: The prototropic exchange rates measured for the 4 investigated iodinated molecules showed strong pH dependence with base catalyzed exchange rate that was faster for monomeric compounds (20-4000 Hz in the pH range of 5.5-7.9). Computed tomography quantification showed marked (up to 2 mg I/mL concentration) and prolonged accumulation (up to 30 minutes postinjection) inside tumor regions. Among the 4 agents we tested, iohexol and ioversol display good CEST contrast properties at 7 T, and in vivo results confirmed strong and prolonged contrast enhancement of the tumors, with elevated extravasation fractions (74%-91%). A strong and significant correlation was found between CT and CEST-MRI tumor-enhanced images (R = 0.70, P < 0.01). CONCLUSIONS: The obtained results demonstrate that iohexol and ioversol, 2 commonly used radiographic compounds, can be used as MRI perfusion agents, particularly useful when serial images acquisitions are needed to complement CT information.

A novel, simple and inexpensive procedure for the simultaneous determination of iopamidol and p-aminohippuric acid for renal function assessment from plasma samples in awake rats.

The purpose of the current study was to design, validate and implement a novel analytical method for the simultaneous plasma measurement of iopamidol and p-aminohippuric acid (PAH) to estimate renal function in awake rats. A reverse-phase high performance liquid chromatographic (RP-HPLC) method for the simultaneous measurement of iopamidol (for glomerular filtration rate estimation, GFR) and PAH (for tubular secretion determination, TS) was designed and validated using a C-18 column, 0.1M acetic acid-10% acetonitrile (90:10, v/v) as mobile phase, at a flow rate of 0.3 ml/min, and UV detection at 270 nm. Iopamidol (244.8 mg/kg) was administered intravenously followed immediately by sodium PAH (100 mg/kg) to healthy female Sprague-Dawley rats. Plasma samples obtained at 2.5, 5, 10, 15, 20, 30, 45, 60, 90, and 120 min after drug administration were deproteinized with 2.5% trichloroacetic acid containing p-aminobenzoic acid as internal standard, and separated by the validated RP-HPLC method described above. The iopamidol and PAH chromatographic data were analyzed using a non-compartmental model. The results demonstrated that the RP-HPLC method was linear in ranges between 15-120 µg/ml and 2.5-120 µg/ml for iopamidol and PAH, respectively. Precision and accuracy were within 15% for both drugs. Recovery of iopamidol and PAH was 92% and 100%, respectively. Plasma iopamidol and PAH clearances in awake rats, estimates for GFR and TS, respectively, were 1.49±0.20 ml/min and 3.73±0.38 ml/min. In conclusion, the method here described is a simple and reliable procedure, for the simultaneous and time-saving determination of GFR and TS from plasma samples in the conscious rat.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy.

INTRODUCTION: Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. OBJECTIVE: The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. MATERIALS AND METHODS: The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. RESULTS: Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. CONCLUSION: The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy / Costo-efectividad de medios de contraste isoosmolales e hiposmolales en pacientes con alto riesgo de nefropatía inducida por medio de contraste

Introduction. Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. Objective. The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. Materials and methods. The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. Results. Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. Conclusion. The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Introducción. Los medios de contraste pueden provocar falla renal aguda por toxicidad directa sobre las células tubulares e isquemia medular renal. Los pacientes diabéticos y los hospitalizados presentan mayor riesgo de desarrollar nefropatía inducida por medios de contraste que la población general. Objetivo. Establecer el costo-efectividad de los medios de contraste isosmolales e hiposmolales en pacientes con alto riesgo. Materiales and métodos. El análisis se basó en una revisión sistemática de la literatura científica, comparando los efectos nefrotóxicos de los medios isosmolales e hipoosmolales. Se consideraron sólo los costos directos, obtenidos del manual tarifario. Se calcularon las tasas del incremento del costo-efectividad, las curvas de eficiencia y de aceptabilidad. Se hicieron análisis univariados de sensibilidad para costos y efectos, así como probabilísticos. Se aplicaron tasas de descuento de 0 y 3 % a los resultados. Se usó como umbral de costo-efectividad por año de vida ganado, el producto interno bruto per cápita. Resultados. Las alternativas con Iopamidol y Iodixanol dominan a las demás porque reducen el riesgo de nefropatía inducida por contraste a un menor costo. La razón del incremento del costo-efectividad del iodixanol comparado con el iopamidol es de US$ 14.660 por año de vida ganado que más que duplica el umbral. Conclusión. El medio de baja osmolalidad, iopamidol, parece ser costo-efectivo comparado con iohexol u otros medios hiposmolares (iopromide, iobitridol, iomeprol, iopentol y ioxilan), en pacientes con alto riesgo de nefropatía inducida por contraste. La elección del medio hiposmolar, depende de la disponibilidad a pagar o del costo por ampolleta.