Packaging and storage—
Preserve in well-closed, light-resistant containers. Store at 25
, excursions permitted between 15
and 30
.
Identification—
B:
Heat about 500 mg in a suitable crucible: violet vapors are evolved.
C:
The retention time of the major peak in the chromatogram of the Test solution corresponds to that observed in the chromatogram of the System suitability solution, as obtained in the test for Related compounds.
Specific rotation 
781S
:
between
4.6
and
5.2
(
t = 20
;
= 436 nm).
Test solution:
400 mg per mL, in water, heating on a water bath, if necessary to effect solution, and passing through a membrane filter having a 3-µm or finer porosity.
Free aromatic amine—
Transfer 500 mg to a 25-mL volumetric flask, and add 20 mL of water, heating on a water bath, if necessary, to effect solution. To a second 25-mL volumetric flask transfer 18.4 mL of water and 1.6 mL of a Standard solution prepared by dissolving a suitable quantity of
USP Iopamidol Related Compound A RS in water and diluting with water to obtain a solution having a concentration of 62.5 µg per mL. To a third 25-mL volumetric flask add 20 mL of water to provide a blank. Treat each flask as follows. Place the flasks in an ice bath, protected from light, for 5 minutes.
[NOTE—In conducting the following steps, keep the flasks in the ice bath and protected from light as much as possible until all of the reagents have been added.
] Add slowly 1 mL of hydrochloric acid, mix, and allow to stand for 5 minutes. Add 1 mL of sodium nitrite solution (1 in 50), mix, and allow to stand for 5 minutes. Add 1 mL of ammonium sulfamate solution (3 in 25), shake, and allow to stand for 5 minutes.
[Caution—Considerable pressure is produced.
] Add 1 mL of
N-(1-naphthyl)ethylenediamine dihydrochloride solution (1 in 1000), and mix. Remove the flasks from the ice bath, and allow to stand in a water bath at about 25
for 10 minutes. Dilute with water to volume, mix, and without delay (about 5 minutes from final dilution), concomitantly determine the absorbances of the solution from the substance under test and the Standard solution in 1-cm cells at the wavelength of maximum absorbance at about 500 nm, with a suitable spectrophotometer, against the prepared blank. The absorbance of the solution from the Iopamidol is not greater than that of the Standard solution (0.02%).
Free iodine—
Transfer 2.0 g to a stoppered, 50-mL centrifuge tube, add sufficient water to dissolve, heating on a water bath, if necessary, to effect solution, and dilute with water to 25 mL. Add 5 mL of toluene and 5 mL of 2 N sulfuric acid, shake well, and centrifuge: the toluene layer shows no red color.
Limit of free iodide—
Transfer about 6.0 g, accurately weighed, to a suitable container, dissolve in 50 mL of water, and add 2.0 mL of 0.001 M potassium iodide. Titrate with 0.001 N silver nitrate VS, determining the endpoint potentiometrically, using a silver indicator electrode and an appropriate reference electrode. Perform a blank determination, and make any necessary correction. Each mL of 0.001 N silver nitrate is equivalent to 126.9 µg of iodide. Not more than 0.001% is found.
Free acid or alkali—
Dissolve 10.0 g in 100 mL of freshly boiled and cooled water. Using a pH meter and a glass-calomel electrode system, determine the volume of 0.01 N hydrochloric acid VS or 0.01 N sodium hydroxide VS to bring the pH of the test solution to 7.0: not more than 1.37 mL of 0.01 N sodium hydroxide, equivalent to a free acid content of 5 mg of hydrochloric acid per 100 g, or not more than 0.75 mL of 0.01 N hydrochloric acid, equivalent to a free alkali content of 3 mg of sodium hydroxide per 100 g, is required.
Heavy metals, Method II 231:
not more than 0.001%.
Related compounds—
Solution A—
Use water.
Solution B—
Prepare a filtered and degassed mixture of water and methanol (3:1).
Mobile phase—
Use variable mixtures of Solution A and Solution B as directed under Chromatographic system.
Test solution—
Transfer about 1.0 g of Iopamidol, accurately weighed, to a 100-mL volumetric flask, add water to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 240-nm detector and a 4.6-mm × 25-cm stainless steel column that contains 5-µm packing L1. The column temperature is maintained at 35
, and the flow rate is about 1.5 mL per minute. The chromatograph is programmed to provide variable mixtures of
Solution A and
Solution B, the percentage of
Solution B being 8.0% at the time of injection, and is held at that percentage for 6 minutes, then increased linearly to 35.0% at 18 minutes, after which it is changed to increase linearly to 92.0% at 30 minutes, maintained at that percentage for 4 minutes, and decreased linearly to 8.0% at 36 minutes, where it is held to the end of the run at 40 minutes. Chromatograph the
System suitability solution, and record the peak responses as directed for
Procedure: the resolution,
R, between iopamidol related compound B and iopamidol is not less than 7.
Procedure—
Separately inject equal volumes (about 20 µL) of the
System suitability solution and the
Test solution into the chromatograph, record the chromatograms, and measure the areas of the peak responses. Calculate the percentage of each related compound in the portion of Iopamidol taken by the formula:
0.10(ri / rs),
in which
ri is the peak response for the individual related compound obtained from the
Test solution; and
rs is the peak response for iopamidol related compound B obtained from the
System suitability solution. The sum of all related compounds does not exceed 0.25%.
Assay—
Transfer about 300 mg of Iopamidol, accurately weighed, to a glass-stoppered, 125-mL conical flask, add 40 mL of 1.25 N sodium hydroxide and 1 g of powdered zinc, connect the flask to a reflux condenser, and reflux the mixture for 30 minutes. Cool the flask to room temperature, rinse the condenser with 20 mL of water, disconnect the flask from the condenser, and filter the mixture. Rinse the flask and the filter thoroughly, adding the rinsings to the filtrate. Add 5 mL of glacial acetic acid, and titrate with 0.1 N silver nitrate VS, determining the endpoint potentiometrically. Each mL of 0.1 N silver nitrate is equivalent to 25.90 mg of C17H22I3N3O8.
;)
