C11H9I3N2O4 613.91

Benzoic acid,3-(acetylamino)-2,4,6-triiodo-5-[(methylamino)carbonyl]-.
5-Acetamido-2,4,6-triiodo-N-methylisophthalamic acid [2276-90-6].

Packaging and storage— Preserve in well-closed containers.Store at 25,excursions permitted between 15and 30.

USP Reference standards á11ñ— USP5-Amino-2,4,6-triiodo-N-methylisophthalamic Acid RS.USP Iothalamic Acid RS.

Identification—

Water,Method Iá921ñ: not more than 1.0%.

Residue on ignition á281ñ: not more than 0.1%.

Free aromatic amine— Dissolve 10.0g of Iothalamic Acid in a minimal amount of 1Nsodium hydroxide in a 150-mLbeaker,add 75mLof water,and adjust with 1Nsulfuric acid to a pHof 7±0.1.Transfer the solution to a 100-mLcylinder,dilute with water to 100mL,and mix.Pipet 5mLof this solution into a 50-mLvolumetric flask,and add 10mLof water.In another flask place 15mLof water to provide a blank,and to a third flask add 12.5mLof water and 2.5mLof a Standard solution prepared as follows.Dissolve 25.0mg of USP5-Amino-2,4,6-triiodo-N-methylisophthalamic Acid RS,accurately weighed,in a mixture of 0.5mLof 1Nsodium hydroxide and 2.5mLof water in a 250-mLbeaker,swirling to effect solution,then add 225mLof water,mix,adjust with 1Nsulfuric acid to a pHof 7±0.1,transfer to a 250-mLvolumetric flask,add water to volume,and mix.Place the three flasks containing the solutions from the substance under test,the Standard solution,and the blank,respectively,in an ice bath.[NOTE—In conducting the following steps,keep the flasks in the ice bath and in the dark as much as possible,until all of the reagents have been added.Chill all reagents and the diluting water to about 5prior to addition.]Treat each flask as follows.Add 5mLof freshly prepared sodium nitrite solution (1in 200),immediately add 10mLof 1Nhydrochloric acid,and swirl gently to mix.[NOTE—Disregard any precipitate that may be formed at this point.]Allow to stand for 2minutes,accurately timed.Add 10mLof ammonium sulfamate solution (1in 50),and shake frequently during 5minutes.Five minutes after the addition of the ammonium sulfamate solution,add 3drops of a 1in 10solution of 1-naphthol in alcohol.Mix,and allow to stand for 1minute.Add 3.5mLof a pH10buffer (made by dissolving 67.5g of ammonium chloride in 300mLof water,adding 570mLof ammonium hydroxide,and diluting with water to 1L).Mix,remove from the ice bath,and immediately dilute,with water that has been chilled to 5,to volume.Within 20minutes of diluting the contents of all three flasks to 50mL,concomitantly determine the absorbances of the test solution and the Standard solution in 1-cm cells at the wavelength of maximum absorbance at about 485nm,with a suitable spectrophotometer,versus the prepared blank.The absorbance of the solution from the Iothalamic Acid is not greater than that of the Standard solution (0.05%).

Iodine and iodide—

Heavy metals á231ñ— To a 50-mLcolor-comparison tube transfer 5.0mLof solution prepared as directed for Test solutionin the test for Iodine and iodide,add 5mLof 1Nsodium hydroxide,dilute with water to 40mL,and mix.Using this as the Test preparation,proceed as directed in the test for Heavy metalsunder Diatrizoate Meglumine:the limit is 0.002%.

Assay— Transfer about 400mg of Iothalamic Acid,accurately weighed,to a glass-stoppered,125-mLconical flask,add 12mLof 5Nsodium hydroxide,20mLof water,and 1g of powdered zinc,connect the flask to a reflux condenser,and reflux for 30minutes.Cool the flask to room temperature,rinse the condenser with 20mLof 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 40mLof 2Nsulfuric acid,and titrate immediately with 0.05Nsilver nitrate VS,determining the endpoint potentiometrically,using silver-calomel electrodes and an agar-potassium nitrate salt bridge.Each mLof 0.05Nsilver nitrate is equivalent to 10.23mg of C11H9I3N2O4.

Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents

USP28–NF23Page 1053

Phone Number:1-301-816-8305