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.

Theoretical B3LYP Study on Electronic Structure of Contrast Agent Iopamidol.

Nonionic low-osmolar contrast agents are thought about safe for intravenous or intra-arterial administration. Iopamidol is one of the contrast agents used for diagnostic clinical computed tomography (CT) protocols last four decades years.The molecular structure of Iopamidol was calculated by the B3LYP density functional model with the LANL2DZ basis set by the Gaussian program. The natural bond orbital analysis in terms of the hybridization of atoms and the electronic structure of the title molecule have been analyzed by using the data obtained from the quantum chemical results. First-order hyperpolarizability (ßtot), the dipole moment (µ) and polarizability (α) and anisotropic polarizability (∆α) of the molecule have been reported. HOMO and LUMO energies and parameters related to energies, and dipole moment, polarizability and hyperpolarizability show minor dependences on the solvent polarity. The hardness of Iopamidol decreases with increasing solvent polarity. The stability of the Iopamidol contrast agent with the hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital analysis. In addition, thermodynamic properties were obtained in the range of 200-1000 K.

Prospective safety evaluation of automated iomeprol 400 injections for CT through peripheral venous cannulas.

AIM: To evaluate prospectively the safety of contrast medium injection through standard peripheral intravenous cannulas at standard injection sites during clinical routine using iomeprol 400, a contrast agent with high viscosity. MATERIALS AND METHODS: Three thousand, five hundred and fourteen clinical CT examinations undertaken at Saarland University Medical Center were included in this prospective observational trial. The size and site of the cannula as well as the contrast medium injection rate and volume were assessed for each patient. In addition, the ability to aspirate blood though the cannula and the occurrence of complications, such as extravasation or abortion of injection by the automated injector, were recorded. RESULTS: The overall complication rate was 30/3,514 (0.85%). With 22 G cannulas, the complication rate was 8/541 (1.48%) applying flow rates of 1-3.5 ml/s (mean 2.1 ml/s). With 20 G cannulas, complications occurred in 21/2,601 cases (0.81%) with flow rates of 1.5-5 ml/s (mean 3 ml/s). The complication rate using 18 G cannulas was 1/377 (0.26%) for flow rates of 2-6 ml/s (mean 3.5 ml/s). No relationship between the site and size of the cannula to the occurrence of complications was found. The inability to aspirate blood correlated with the development of extravasation. CONCLUSIONS: The injection of contrast agent using standard peripheral venous cannulas is a safe and reliable procedure yielding diagnostic image contrast, even when using highly viscous contrast agents such as iomeprol 400; an aspiration test should be performed before each injection.

Effect of low tube voltage and low iodine concentration abdominal CT on image quality and radiation dose in children: preliminary study.

PURPOSE: To evaluate the image quality of a double-low protocol (low tube voltage and low iodine concentration) for abdominal CT in children. MATERIALS AND METHODS: The double-low protocol was compared to the conventional protocol in pediatric patients weighing less than 40 kg from May 2016 to December 2016. Double-low protocol (Group A, n = 18): tube voltage, 70 kVp; and iodine concentration,: 250 mgI/mL versus Conventional protocol (Group B, n = 13): tube voltage, 80-100 kVp; and iodine concentration, 350 mgI/mL. Mean attenuation, noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared between the two groups. Image contrast, noise, beam-hardening artifacts, and overall image quality were subjectively scored. Reader performance for correctly differentiating two groups by visual assessment was evaluated. Radiation dose and total iodine load were recorded. RESULTS: The mean attenuations of the portal vein and liver and the mean image noise in Group A were higher than in Group B (p = 0.04, 0.03, 0.004, respectively). The mean SNR and CNR of the main portal vein and liver were lower in Group A without any statistically significant difference. There were no statistically significant differences between the two groups in qualitative analysis (image contrast, image noise, and overall image quality) with substantial agreement between the reviewers (weighted kappa values; 0.59-0.76). Significantly diminished radiation dose and iodine load were observed in Group A compared with Group B (25.0%, 36.8% reduction; p = 0.007, 0.006, respectively). CONCLUSION: The double-low protocol was feasible for pediatric abdominal CT and reduced both radiation dose and iodine load, while maintaining image quality.

Impact of chlorine exposure time on disinfection byproduct formation in the presence of iopamidol and natural organic matter during chloramination.

Chloramines, in practice, are formed onsite by adding ammonia to chlorinated drinking water to achieve the required disinfection. While regulated disinfection byproducts (DBPs) are reduced during chloramine disinfection, other DBPs such as iodinated (iodo-) DBPs, that elicit greater toxicity are formed. The objective of this study was to investigate the impact of prechlorination time on the formation of both halogen-specific total organic halogen (TOX) and iodo/chlorinated (chloro-) DBPs during prechlorination/chloramination in source waters (SWs) containing iopamidol, an X-ray contrast medium. Barberton SW (BSW) and Cleveland SW (CSW) containing iopamidol were prechlorinated for 5-60 min and afterwards chloraminated for 72 hr with ammonium chloride. Chlorine contact time (CCT) did not significantly impact total organic iodine (TOI) concentrations after prechlorination or chloramination. Concentrations of total organic chlorine (TOCl) formed during prechlorination did not significantly change regardless of pH and prechlorination time, while TOCl appeared to decrease after 72 hr chloramination period. Dichloroiodomethane (CHCl2I) formation during prechlorination did not exhibit any significant trends as a function of pH or CCT, but after chloramination, significant increases were observed at pHs 6.5 and 7.5 with respect to CCT. Iodo-HAAs were not formed during prechlorination but were detected after chloramination. Significant quantities of chloroform (CHCl3) and trichloroacetic acid (TCAA) were formed during prechlorination but formation ceased upon ammonia addition. Therefore, prechlorination studies should measure TOX and DBP concentrations prior to ammonia addition to obtain data regarding the initial conditions.

Abiotic reductive deiodination of iodinated organic compounds and X-ray contrast media catalyzed by free corrinoids.

Iodinated X-ray contrast media are known for their stability concerning deiodination in the aquatic environment under aerobic conditions. In this study, we demonstrate the abiotic reductive deiodination of the iodinated contrast media iopromide, iopamidol and diatrizoate in the presence of corrinoids. In addition, triiodinated benzoic acid derivatives with iodine atoms bound at different positions were investigated. Corrinoids like cyanocobalamin (vitamin B12) and dicyanocobinamide served as electron shuttles and as catalysts between the reducing agent (e.g., titanium (III) citrate) and the electron accepting iodinated compound. The concentration decrease of the iodinated compounds followed first-order kinetics with rate constant kobs depending on the iodinated compound. A linear correlation between the rate of iodide release and the corrinoid concentration was observed, with deiodination rates for dicyanocobinamide twice as high as for vitamin B12. Reducing agents with a less negative standard redox potential like dithiothreitol or cysteine caused slower deiodination as the cobalt center was only reduced to its CoII oxidation state. With a temperature increase from 11 to 23 °C, the concentrations of released iodide doubled. A complete deiodination was only observed for the iodinated contrast media but not for structurally similar iodinated benzoic acid derivatives.

Degradation of iopamidol by three UV-based oxidation processes: Kinetics, pathways, and formation of iodinated disinfection byproducts.

In this study, the degradation kinetics of iopamidol (IPM) by three different UV-based oxidation processes including UV/hydrogen peroxide (H2O2), UV/persulfate (PDS) and UV/chlorine (NaClO) were examined and the potential formation of iodinated disinfection byproducts (I-DBPs) in these processes followed by sequential chlorination was comparatively investigated. Increasing pH led to the decrease of IPM degradation rate in UV/NaClO, while it showed negligible impact in UV/PDS and UV/H2O2. Common background constituents such as chloride ions (Cl-), carbonate (HCO3-) and natural organic matter (NOM) inhibited IPM degradation in UV/H2O2 and UV/PDS, while IPM degradation in UV/NaClO was only suppressed by NOM but not Cl- and HCO3-. The differences in transformation products of IPM treated by hydroxyl radical (HO*), sulfate radical (SO4*-), as well as Cl2*- and ClO* generated in these processes, respectively, were also analyzed. The results suggested that hydroxyl radical (HO*) preferred to form hydroxylated derivatives. Sulfate radical (SO4*-) preferred to oxidize amino group of IPM to nitro group, while Cl2*- and ClO* favored the generation of chlorine-containing products. Moreover, specific I-DBPs (i.e., iodoform (IF) and monoiodacetic acid (MIAA)) were detected in the three processes followed by chlorination. The addition of NOM had little effect on IF formation of three processes, while MIAA formation decreased in all processes except UV/H2O2. Given that the formation of I-DBPs in UV/NaClO was less than those formed in the other two processes, UV/NaClO seems to be a more promising strategy for effectively removing IPM with alleviation of I-DBPs in treated water effluents.

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.

Electrochemical reductive dehalogenation of iodine-containing contrast agent pharmaceuticals: Examination of reactions of diatrizoate and iopamidol using the method of rotating ring-disc electrode (RRDE).

This study examined the electrochemical (EC) reduction of iodinated contrast media (ICM) exemplified by iopamidol and diatrizoate. The method of rotating ring-disc electrode (RRDE) was used to elucidate rates and mechanisms of the EC reactions of the selected ICMs. Experiments were carried at varying hydrodynamic conditions, concentrations of iopamidol, diatrizoate, natural organic matter (NOM) and model compounds (resorcinol, catechol, guaiacol) which were used to examine interactions between products of the EC reduction of ICMs and halogenation-active species. The data showed that iopamidol and diatrizoate were EC-reduced at potentials < -0.45 V vs. s.c.e. In the range of potentials -0.65 to -0.85 V their reduction was mass transfer-controlled. The presence of NOM and model compounds did not affect the EC reduction of iopamidol and diatrizoate but active iodine species formed as a result of the EC-induced transformations of these ICMs reacted readily with NOM and model compounds. These data provide more insight into the nature of generation of iodine-containing by-products in the case of reductive degradation of ICMs.

Formation of DBPs and halogen-specific TOX in the presence of iopamidol and chlorinated oxidants.

Iopamidol is a known direct precursor to iodinated and chlorinated DBP formation; however, the influence of iopamidol on both iodo/chloro-DBP formation has yet to be fully investigated. This study investigated the effect of iopamidol on the formation and speciation of halogen-specific total organic halogen (TOX), as well as iodo/chloro-DBPs, in the presence of 3 source waters (SWs) from Northeast Ohio and chlorinated oxidants. Chlorination and chloramination of SWs were carried out at pH 6.5-9.0 and, different iopamidol and dissolved organic carbon (DOC) concentrations. Total organic iodine (TOI) loss was approximately equal (22-35%) regardless of SW. Total organic chlorine (TOCl) increased in all SWs and was substantially higher in the higher SUVA254 SWs. Iopamidol was a direct precursor to chloroform (CHCl3), trichloroacetic acid (TCAA), and dichloroiodomethane (CHCl2I) formation. While CHCl3 and TCAA exhibited different formation trends with varying iopamidol concentrations, CHCl2I increased with increasing iopamidol and DOC concentrations. Low concentrations of iodo-acids were detected without discernible trends. Total trihalomethanes (THMs), total haloacetic acids (HAAs), TOCl, and unknown TOCl (UTOCl) were correlated with fluorescence regional volumes and SUVA254. The yields of all these species showed a strong positive correlation with fulvic, humic, and combined humic and fulvic regions, as well as SUVA254. Iopamidol was then compared to the 3 SWs with respect to DBP yield. Although the SUVA254 of iopamidol was relatively high, it did not produce high yields of THMs and HAAs compared to the 3 SWs. However, chlorination of iopamidol did result in high yields of TOCl and UTOCl.

Deiodination of iopamidol by zero valent iron (ZVI) enhances formation of iodinated disinfection by-products during chloramination.

Iodinated X-ray contrast media (ICM) is considered as one of iodine sources for formation of toxic iodinated disinfection byproducts (I-DBPs) during disinfection. This study investigated transformation of a typical ICM, iopamidol (IPM) by zero valent iron (ZVI) and the effect of transformation on the formation of I-DBPs during chloramination. It was found that the presence of ZVI could deiodinate IPM into I- and the transformation of IPM exhibited a pseudo-first-order kinetics. Acidic circumstance, SO42-, Cl- and monochloramine could promote the transformation of IPM by ZVI, while SiO32- inhibited the transformation of IPM. Moreover, the transformation of IPM by ZVI changed both the formed species and amounts of I-DBPs during chloramination. During the chloramination of IPM-containing water, CHCl2I and iodoacetic acid were the predominant iodinated trihalomethanes (I-THMs) and iodinated haloacetic acids (I-HAAs), respectively in the absence of ZVI, while CHI3 and triiodoacetic acid became the predominant ones with 1.0 g L-1 ZVI. The addition of 5.0 g L-1 ZVI increased I-DBPs formation amounts by 6.0 folds after 72 h and maximum formation of I-DBPs occurred at pH 5.0. Enhanced I-DBPs formation was also observed with various real water sources. Given that ZVI ubiquitously exists in the unlined cast iron distribution pipes, the deiodination of IPM by ZVI during distribution may increase the formation of I-DBPs, which needs receive enough attention.

Oxidation of iopamidol with ferrate (Fe(VI)): Kinetics and formation of toxic iodinated disinfection by-products.

Presence of iodinated X-ray contrast media (ICMs) in source water is of high concern, because of their potential to form highly toxic iodinated disinfection by-products (I-DBPs). This study investigated kinetics, mechanisms and products for oxidation of one ICMs, iopamidol (IPM) by ferrate (Fe(VI)). The obtained apparent second-order rate constants for oxidation of IPM by Fe(VI) ranged from 0.7 M-1 s-1 to 74.6 M-1 s-1 at pH 6.0-10.0, which were highly dependent on pH. It was found that the oxidation of IPM by Fe(VI) led to the formation of highly toxic I-DBPs. Iodoform (IF), iodoacetic acid and triiodoacetic acid formations were observed during the oxidation and IF dominated the formed I-DBPs. The formation of I-DBPs was also governed by pH and the maximum formation of I-DBPs occurred at pH 9.0. Transformation pathways of IPM by Fe(VI) oxidation were speculated to proceed through deiodination, amide hydrolysis and oxidation of amine reactions. The deiodination reaction during the oxidation of IPM by Fe(VI) contributed to the formation of I-DBPs. The formation of I-DBPs during the oxidation of IPM by Fe(VI) was significantly higher than those of iohexol, diatrizoate and iopromide, which was consistent with the lowest molecular orbital energy gap of IPM. Although Fe(VI) is considered as a green oxidant, the formation of highly toxic I-DBPs during the oxidation of IPM should receive great attention.

The Influence of Contrast Agent's Osmolarity on Iodine Delivery Protocol in Coronary Computed Tomography Angiography: Comparison Between Iso-Osmolar Iodixanol-320 and Low-Osmolar Iomeprol-370.

OBJECTIVES: This study aims to assess whether iodine-contained contrast agents with different osmolarity affect iodine delivery protocol during coronary computed tomography angiography (CCTA). METHODS: Patients who underwent CCTA were randomized to receive contrast media either iodixanol-320 (iso-osmolar group) or iopromide-370 (low-osmolar group). Contrast protocols were recorded. Tube voltage of 100 kV was chosen for patients with body mass index of less than or equal to 25 (n = 224) and tube voltage of 120 kV for patients with body mass index of greater than 25 (n = 165). Both groups applied automatic current modulation technique. Mean contrast enhancement of the ascending aorta, left main coronary artery, and descending aorta was calculated. Simulated contrast flow rate and iodine delivery rate (IDR) to reach a mean contrast enhancement level of 350 HU were calculated. RESULTS: A total of the 389 patients were enrolled in the study. To achieve the same contrast enhancement of 350 HU, iso-osmolar group required higher simulated contrast flow rate (3.90 vs 3.62 mL/s, P = 0.017) but lower simulated IDR (1.34 vs 1.25 g/s, P = 0.024) compared with low-osmolar group. CONCLUSIONS: To maintain a similar level of contrast enhancement during CCTA, iodixanol-320 needs larger contrast flow rate with lower IDR compared with low-osmolar iopromide-370.

The impact of iodinated X-ray contrast agents on formation and toxicity of disinfection by-products in drinking water.

The presence of iodinated X-ray contrast media (ICM) in source waters is of high concern to public health because of their potential to generate highly toxic disinfection by-products (DBPs). The objective of this study was to determine the impact of ICM in source waters and the type of disinfectant on the overall toxicity of DBP mixtures and to determine which ICM and reaction conditions give rise to toxic by-products. Source waters collected from Akron, OH were treated with five different ICMs, including iopamidol, iopromide, iohexol, diatrizoate and iomeprol, with or without chlorine or chloramine disinfection. The reaction product mixtures were concentrated with XAD resins and the mammalian cell cytotoxicity and genotoxicity of the reaction mixture concentrates was measured. Water containing iopamidol generated an enhanced level of mammalian cell cytotoxicity and genotoxicity after disinfection. While chlorine disinfection with iopamidol resulted in the highest cytotoxicity overall, the relative iopamidol-mediated increase in toxicity was greater when chloramine was used as the disinfectant compared with chlorine. Four other ICMs (iopromide, iohexol, diatrizoate, and iomeprol) expressed some cytotoxicity over the control without any disinfection, and induced higher cytotoxicity when chlorinated. Only iohexol enhanced genotoxicity compared to the chlorinated source water.

Chlor(am)ination of iopamidol: Kinetics, pathways and disinfection by-products formation.

The degradation kinetics, pathways and disinfection by-products (DBPs) formation of iopamidol by chlorine and chloramines were investigated in this paper. The chlorination kinetics can be well described by a second-order model. The apparent second-order rate constants of iopamidol chlorination significantly increased with solution pH. The rate constants of iopamidol with HOCl and OCl- were calculated as (1.66 ± 0.09) × 10-3 M-1 s-1 and (0.45± 0.02) M-1 s-1, respectively. However, the chloramination of iopamidol fitted well with third-order kinetics and the maximum of the apparent rate constant occurred at pH 7. It was inferred that the free chlorine (i.e., HOCl and OCl-) can react with iopamidol while the combined chlorine species (i.e., NH2Cl and NHCl2) were not reactive with iopamidol. The main intermediates during chlorination or chloramination of iopamidol were identified using ultra performance liquid chromatography - electrospray ionization-mass spectrometry (UPLC-ESI-MS), and the destruction pathways including stepwise deiodination, hydroxylation as well as chlorination were then proposed. The regular and iodinated DBPs formed during chlorination and chloramination of iopamidol were measured. It was found that iodine conversion from iopamidol to toxic iodinated DBPs distinctly increased during chloramination. The results also indicated that although chloramines were much less reactive than chlorine toward iopamidol, they led to the formation of much more toxic iodinated DBPs, especially CHI3.

Techniques to Form a Suitable Lipiodol-Epirubicin Emulsion by Using 3-Way Stopcock Methods in Transarterial Chemoembolization for Liver Tumor.

PURPOSE: To compare physicochemical properties of emulsions of ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and epirubicin prepared using different techniques for conventional transarterial chemoembolization. MATERIALS AND METHODS: Lipiodol was mixed with epirubicin solution (8.33 mg/mL) by using a 3-way stopcock. The following technical parameters were compared: ratio of epirubicin solution to Lipiodol (1:2 vs 1:1), number of pumping exchanges through the stopcock (20 exchanges vs 10 exchanges), pumping speed (1 s/push vs 2 s/push), and first push syringe (epirubicin solution vs Lipiodol). RESULTS: The mean percentage of water-in-oil was 70.45 ± 1.51 in the 1:2 epirubicin-Lipiodol ratio and 16.03 ± 2.95 in the 1:1 ratio (P < .001). The first push syringe did not influence emulsion type. Median droplet sizes were significantly larger in the slower pumping speed (52.0 µm in 2 s vs 33.7 µm in 1 s; P < .001), whereas there was no significant difference in number of pumping exchanges. Droplet sizes enlarged during 30 minutes after pumping. Viscosity was lower in the 1:1 ratio and the slower pumping speed. Viscosity decreased during 30 minutes after pumping. CONCLUSIONS: The ratio of epirubicin to Lipiodol is a significant factor to form water-in-oil emulsions with higher viscosity. The percentage of water-in-oil is limited to 70% using current pumping techniques. The pumping speed strongly influences droplet size and viscosity.

Effects of two types of medical contrast media on routine chemistry results by three automated chemistry analyzers.

OBJECTIVES: The use of iodinated contrast media has grown in popularity in the past two decades, but relatively little attention has been paid to the possible interferential effects of contrast media on laboratory test results. Herein, we investigate medical contrast media interference with routine chemistry results obtained by three automated chemistry analyzers. METHODS: Ten levels of pooled serum were used in the study. Two types of medical contrast media [Iopamiro (iopamidol) and Omnipaque (iohexol)] were evaluated. To evaluate the dose-dependent effects of the contrast media, iopamidol and iohexol were spiked separately into aliquots of serum for final concentrations of 1.8%, 3.6%, 5.5%, 7.3%, and 9.1%. The 28 analytes included in the routine chemistry panel were measured by using Hitachi 7600, AU5800, and Cobas c702 analyzers. We calculated the delta percentage difference (DPD) between the samples and the control, and examined dose-dependent trends. RESULTS: When the mean DPD values were compared with the reference cut-off criteria, the only uniformly interferential effect observed for all analyzers was in total protein with iopamidol. Two additional analytes that showed trends toward interferential effects only in few analyzers and exceeded the limits of the allowable error were the serum iron and the total CO2. The other combinations of analyzer and contrast showed no consistent dose-dependent propensity for change in any analyte level. CONCLUSIONS: Our study suggests that many of the analytes included in routine chemistry results, except total protein and serum iron, are not significantly affected by iopamidol and iohexol. These results suggest that it would be beneficial to apply a flexible medical evaluation process for patients requiring both laboratory tests and imaging studies, minimizing the need for strict regulations for sequential tests.

Myelography Iodinated Contrast Media. 2. Conformational Versatility of Iopamidol in the Solid State.

The phenomenon of polymorphism is of great relevance in pharmaceutics, since different polymorphs have different physicochemical properties, e.g., solubility, hence, bioavailability. Coupling diffractometric and spectroscopic experiments with thermodynamic analysis and computational work opens to a methodological approach which provides information on both structure and dynamics in the solid as well as in solution. The present work reports on the conformational changes in crystalline iopamidol, which is characterized by atropisomerism, a phenomenon that influences both the solution properties and the distinct crystal phases. The conformation of iopamidol is discussed for three different crystal phases. In the anhydrous and monohydrate crystal forms, iopamidol molecules display a syn conformation of the long branches stemming out from the triiodobenzene ring, while in the pentahydrate phase the anti conformation is found. IR and Raman spectroscopic studies carried out on the three crystal forms, jointly with quantum chemical computations, revealed that the markedly different spectral features can be specifically attributed to the different molecular conformations. Our results on the conformational versatility of iopamidol in different crystalline phases, linking structural and spectroscopic evidence for the solution state and the solid forms, provide a definite protocol for grasping the signals that can be taken as conformational markers. This is the first step for understanding the crystallization mechanism occurring in supersaturated solution of iopamidol molecules.

Iodinated X-ray contrast agents: Photoinduced transformation and monitoring in surface water.

Conventional wastewater treatment methods have shown to be unsuitable for a complete elimination of iodinated X-ray contrast agents (ICMs), which have thus been found in wastewater treatment plant (WWTP) effluent and in surface water. Once in the surface water, they could be transformed through different processes and form several transformation products that may need to be monitored as well. To this end, we studied the abatement and transformation of ICMs by combining laboratory experiments with in field analyses. We irradiated different aqueous solutions of the selected pollutants in the presence of TiO2 as photocatalyst, aimed to promote ICMs degradation and to generate photoinduced transformation products (TPs) similar to those occurring in the environment and effluent wastewater. This experimental strategy has been applied to the study of three ICMs, namely iopromide, iopamidol and diatrizoate. A total of twenty-four, ten, and ten TPs were detected from iopamidol, diatrizoate and iopromide, respectively. The analyses were performed using a liquid chromatography-LTQ-FT-Orbitrap mass spectrometer. The mineralization process and acute toxicity evolution were assessed as well over time and revealed a lack of mineralization for all ICMs and the formation of harmful byproducts. After characterizing these transformation products, WWTP effluent and surface water taken from several branches of the Chicago River were analyzed for ICMs and their TPs. HRMS with MS/MS fragmentation was used as a confirmatory step for proper identification of compounds in water and wastewater samples. All three of ICM were detected in the effluent and surface water samples, while no significant amount of TPs were detected.

Use of orbitrap-MS/MS and QSAR analyses to estimate mutagenic transformation products of iopamidol generated during ozonation and chlorination.

The effects of two water purification processes (ozonation, and chlorination after ozonation) on the mutagenicity of a solution containing iopamidol (X-ray contrast medium) were investigated by using the Ames assay. No mutagenicity was observed during ozonation. In contrast, mutagenicity was induced by the ozone-treated iopamidol-containing solution after subsequent chlorination, indicating that mutagenic transformation-products (TPs) were generated. Ten of 70 peaks detected on the LC/MS total ion chromatogram (TIC) of the ozone-treated iopamidol-containing solution after chlorination had a positive correlation (r(2) > 0.6) between their peak areas and the observed mutagenicity, suggesting that TPs detected as these peaks may induce mutagenicity. To narrow down the possible contributors to the observed mutagenicity, we compared the areas of the peaks on the TIC-charts with and without chlorination. Of the ten peaks, six were also detected in the ozone-treated iopamidol-containing solution without chlorination, which did not induce mutagenicity, indicating that these peaks were not related to the observed mutagenicity. Accurate m/z values and MS/MS analysis with an orbitrap MS of the remaining four peaks revealed that two of them represented the same TP in the negative and positive ion modes. The three remaining TPs were assessed in four quantitative structure-activity relationship models for predicting Ames mutagenicity. At least one model predicted that two of the three TPs were mutagenic, whereas none of the models predicted that the other TP was a mutagen, suggesting that the former TPs, estimated as N1-acetyl-5-amino-6-chloro-2-iodobenzene-1,3-dicarboxamide and 3-hydroxy-2-{3-[(2-hydroxyethoxy)carbonyl]-2,4,6-triiodo-5-nitrobenzoyl}amino)propanoic acid, could be the candidate compounds that contributed to the observed mutagenicity.