A comparative study between three stability indicating spectrophotometric methods for the determination of diatrizoate sodium in presence of its cytotoxic degradation product based on two-wavelength selection.

Three sensitive, selective, and precise stability indicating spectrophotometric methods for the determination of the X-ray contrast agent, diatrizoate sodium (DTA) in the presence of its acidic degradation product (highly cytotoxic 3,5-diamino metabolite) and in pharmaceutical formulation, were developed and validated. The first method is ratio difference, the second one is the bivariate method, and the third one is the dual wavelength method. The calibration curves for the three proposed methods are linear over a concentration range of 2-24 µg/mL. The selectivity of the proposed methods was tested using laboratory prepared mixtures. The proposed methods have been successfully applied to the analysis of DTA in pharmaceutical dosage forms without interference from other dosage form additives. The results were statistically compared with the official US pharmacopeial method. No significant difference for either accuracy or precision was observed.

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 microg/l could be achieved whereby reproducibility was below 6% for all compounds under investigation.

[The effect of cimetidine on the renal excretion of verografin and iodamide in dogs]. / Vliianie tsimetidina na pochechnuiu ékskretsiiu verografina i iodamida u sobak.

The intravenous injection of cimetidine in a dose of 20 mg/kg enhanced verografine and iodamide excretion in chronic canine experiments. The higher verografine and iodamide excretion was due to their increased renal tubular secretion. In dogs, cimetidine unchanged the secretion of cardiotrast, a test agent for anionic transport. Possible extrarenal mechanisms of action of cimetidine on verografine and iodamide transport were also examined.

Effects of diatrizoate and iopamidol on spermatogenesis.

RATIONALE AND OBJECTIVES: The biological effects of iodinated contrast media were examined by using spermatogenesis in mouse testis as the experimental model. METHODS: Spermhead survival and abnormality assays were used as the biological end points. Diatrizoate meglumine/diatrizoate sodium and iopamidol were administered intravenously at equal rates and concentrations. Testicular uptake and clearance of these contrast agents were examined by high-performance liquid chromatography techniques. Appropriate mannitol solutions were employed as osmolality controls. RESULTS: Intravenous administration of the contrast agent or its respective mannitol control resulted in approximately a 30% decrease in spermhead count. A dose-related experiment with mannitol demonstrated that the spermhead count decreased rapidly until 600 mOsm/kg was reached, beyond which this decrease was minimal. Clearance of both contrast media was complete in approximately 4 hours. No significant increase in the induction of spermhead abnormalities was observed. CONCLUSION: Osmotic substances, such as iodinated contrast agents, affect the process of spermatogenesis.

Assay of radiographic contrast agents in mice plasma and testes by high-performance liquid chromatography.

A new buffer system is reported for the analysis of radiographic contrast agents (RCAs) sodium meglumine diatrizoate, iohexol, and iopamidol in mice plasma and testes, on a reversed-phase HPLC with UV detection. The buffer consisting of 0.1 M NaH2PO4, 0.2 mM Na2EDTA adjusted to pH 3.1 with orthophosphoric acid and 2.5-5.0% acetonitrile (v/v) resolved RCA peaks for clear quantitation. The main advantages of this system are the ambient temperature of operation and direct sample injection without prior sample purification as required in the earlier procedures. Using this procedure, uptake and clearance kinetics of these RCAs were studied in mice plasma and testes, following iv injections via tail veins. The plasma levels of all the RCAs reached maxima between 5 and 15 min and dropped down sharply. At the end of 12 h they were virtually undetected (detection limits 0.64-0.71 micrograms/mL). The testicular levels also showed a similar trend and reached undetectable levels after 4 h. There were no signs of metabolism of these RCAs in plasma or testes. The present clearance kinetics in plasma compares very well with earlier reports of non-HPLC methods of assay.

High performance liquid chromatography with multiwavelength detection: a technique for identification of iodinated x-ray contrast agents in human body fluids and brain tissue.

PURPOSE: Several cases of a severe adverse reaction, referred to as "ascending tonic-clonic seizure syndrome," have been reported after administration of water-soluble iodinated x-ray contrast agents for myelographic examinations. Because of the bizarre reactions, the identities of the causative contrast media were questioned. METHODS: Analyses of biologic materials from four of these patients were performed by using reverse-phase high-performance liquid chromatography. The chromatographic system was equipped with a fast-scanning UV-visible detector for the analysis of the UV-spectra of the chromatographic peaks. RESULTS: The analyses revealed that the nonionic contrast agents iohexol or ioversol were not present in detectable amounts in any of the samples. On the other hand, the chromatographic analyses revealed peaks that cochromatographed with and showed the same UV-spectra as the ionic agents diatrizoate, metrizoate, and ioxitalamate. CONCLUSION: The results indicate inadvertent injection of ionic contrast medium in all four cases.

[The effect of microsomal enzyme inducers on the renal transport of verografin (triombrast)]. / Vliianie induktorov mikrosomal'nykh fermentov na pochechnyi transport verografina (triombrasta).

In experiments on rats and dogs it was shown that administration of phenobarbital (20 and 50 mg/kg orally, 4 days), benzonal (35 mg/kg, orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) caused on the 3rd day following the last administration of the drug a reduction of verografine secretion in the kidneys. After administration of phenobarbital to dogs (20 mg/kg orally, 4 days) a decrease of renal transport of verografine within 4-5 weeks was observed.

[The renal transport of cardiotrast, verografin and iodamide]. / Pochechnyi transport kardiotrasta, verografina i iodamida.

In chronic experiments on dogs it was shown that verografin and iodamide are excreted from the body not only by filtration but by tubular excretion as well. The maximal transport of verografin and iodamide is significantly lower than that of cardiotrast. In experiments on rats similar results were obtained. Concurrent administration of verografin and iodamide with cardiotrast decreases their excretion in the urine in rats that is probably due to competition for the common transport system in the epithelium of renal tubules.

Pulmonary edema following high intravenous doses of ionic contrast media. Effect of the anion composition and concentration.

High intravenous doses of diatrizoate are known to induce a profound degree of pulmonary edema which is dose- and injection rate-dependent in the rat. In this study, meglumine salts of diatrizoate, iothalamate, and metrizoate were evaluated for their capacity to induce pulmonary edema following intravenous injections. Differences in anion composition or concentration of diatrizoate meglumine/sodium salts did not cause significantly different degrees of pulmonary edema.

Absorption of contrast medium during ERCP.

In order to assess systemic absorption, serum diatrizoate levels were measured in 25 patients requiring endoscopic retrograde cholangiopancreatography (ERCP). Urinary diatrizoate was measured in the urine of seven of these. In five additional patients, diatrizoate was instilled into the duodenum during endoscopy. Blood was drawn before and after completion of the procedure in all patients and at intervals from 2 to 24 hr in nine. Eighteen-hour urine collections were obtained from seven patients. Increases in serum diatrizoate concentration were 7.10 micrograms/ml +/- 3.01 (mean +/- SE) in the duodenal-instillation patients, 230.68 +/- 53.24 micrograms/ml in 9 patients in whom only the pancreatic duct was visualized, 7.83 +/- 1.05 micrograms/ml in three patients in whom only the bile duct was visualized, and 77.67 +/- 28.22 micrograms/ml in 13 patients in whom both ducts were visualized. The mean total urinary excretion of diatrizoate was 3.05 +/- 0.98 g of diatrizoate. Endoscopists performing ERCP should be aware of the likelihood of systemic absorption and the possibility of reactions to iodinated contrast materials in sensitive patients.

[The pharmaco-kinetics of angiographic contrast media with special reference to the extravascular space. Experimental studies on dogs. III. Is there an entero-hepatic circulation of angiographic contrast media? A discussion summarising the results of the entire studies (author's transl)]. / Pharmakokinetik angiographischer Kontrastmittel unter besonderer Berücksichtigung des extravasalen Raumes. Eine experimentelle Grundlagenstudie an Hunden zur Charakterisierung der Angiographica. III. Mitteilung: Gibt es einen enterohepatischen Kreislauf angiographischer Kontrasmittel?--Zusammenfassende Diskussion der Ergebnisse aller Versuchsreihen

The presence of an entero hepatic circulation of angiographic contrast media has been demonstrated, but quantitatively it is of little importance. About 1/2% of the contrast reaching the gut in the bile is reabsorbed and after being carried through the portal vein to the liver is re-excreted in the bile. Most of the contrastcontaining bile reaching the small bowel is excreted in the faeces; nearly all of the contrast absorbed from the colon is carried through the portal vein to the liver and after reaching the circulation is excreted by the kidneys.