A simple method for the identification and assay of iopamidol and iothalamate meglumine in pharmaceutical samples based on proton nuclear magnetic resonance spectroscopy.

A proton nuclear magnetic resonance (PMR) spectroscopic method is described for the direct assay and identification of the triiodinated radiographic contrast agents iopamidol (nonionic type) and iothalamate meglumine (ionic type) in commercial solutions and as a bulk material. Samples were prepared by simply diluting an injectable solution with or dissolving a powdered sample in D2O. Sodium acetate was added to serve as an internal standard. Quantitations were based on the resonance signals for the protons of the CH3-CO-group at 1.58 ppm (iopamidol) or 2.25 ppm (iothalamate), CH3-N-group at 2.38 ppm (meglumine) and CH3-CO-group at 1.92 ppm (acetate). The mean +/- SD (n = sets of 10 samples each) recovery of iopamidol, iothalamic acid and meglumine from synthetic mixtures with the internal standard were 99.6 +/- 0.63, 99.7 +/- 0.66 and 99.9 +/- 1.18%, respectively; with the values ranging from 98.7-100.9% for iopamidol and iothalamate, and from 98.3-100.8% for meglumine.

Development of a nonisotopic capillary electrophoresis-based method for measuring glomerular filtration rate.

The conditions for quantitative measurement of nonisotopic iothalamate meglumine (Conray) in urine and plasma by capillary zone electrophoresis (CE) have been developed. The impetus for developing this methodology was to replace the traditional [125I]iothalamate glomerular filtration rate (GFR) marker assay, a routine tool in the measurement of kidney function. This new approach for measuring kidney function is attractive since it avoids the cost of administration of radioisotopic compounds to patients, as well as the cost associated with purchase and disposal of isotopic compounds and contaminated samples. The concentration of iothalamate in urine and plasma determined by CE can be used directly to calculate GFR. The GFR in patients injected with [125I]iothalamate and nonisotopic iothalamate simultaneously showed an excellent correlation (0.998) with between-day coefficient of variation of 2.30% and a recovery of 102% and 98%, respectively, when added to urine and plasma. Interference from drugs and other urinary compounds is eliminated with this method. Collectively, this study has shown that CE is a cost-effective alternative to the current methodology for measuring GFR.

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.

Tissue pertechnetate and iodinated contrast material in ischemic stroke.

Isotope uptake during static radionuclide scanning and contrast enhancement during CT scanning, which may result from similar pathophysiologic mechanisms after ischemic infarction, were investigated in an animal model. Infarction was produced by transorbital occlusion of the middle cerebral artery in cats killed one, 2, 4, 8, or 16 days later. Sodium pertechnetate containing technetium-99m and 30% methylglucamine iothalamate labeled with I-125 were administered intravenously 60 and 15 min respectively prior to sacrifice. A coronal section through the infarct was parceled into 30 portions which were assayed for concentration of each isotope. Adjacent brain was prepared for histopathologic correlation. Concentrations of the 2 materials were highest in infarcted brain at 4 and 8 days. Strong positive correlation was found between tissue concentrations of the 2 materials in all brain samples. Elevated tissue levels correlated with necrosis, macrophage infiltration, and vascular hyperplasia. The results support the probability that radionuclide scan positivity and CT contrast enhancement reflect the same pathophysiologic development, probably extravasation of the respective labels, after ischemic stroke.

Epinephrine enhanced knee arthrography.

The effect of .3 cc of 1:1000 epinephrine on iodine concentration, total iodine content, fluid volume and radiographic quality was evaluated in knee arthrograms in dogs. With the addition of epinephrine the iodine concentration and total iodine content were significantly higher initially and remained significantly higher than in controls over a one hour period. The fluid volume in the knee was significantly lower with epinephrine. Initially both contrast absorption and dilution have major effects in decreasing iodine concentration. With increasing time the effect of contrast absorption becomes the major factor, having a two of three times greater effect on decreasing iodine concentration. With epinephrine radiographs were judged significantly better early and while the quality deteriorated rapidly in the controls the enhanced quality with epinephrine persisted up to one hour. Epinephrine is a very useful adjunct in enhancing the quality of knee arthrography.

Measurement of plasma contrast levels during excretory urography.

Ultraviolet spectrophotometry permits easy measurement of plasma levels of intravenously injected contrast media. The initial results are described from the determination of plasma methylglucamine iothalamate (Conray 60) levels during routine excretory urography in 10 normal patients. This simple procedure has many potential applications in the investigation of contrast media physiology.