Iopamidol
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C17H22I3N3O8 777.09

1,3-Benzenedicarboxamide,N,N¢-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodo-,(S)-.
(S)-N,N¢-bis[2-Hydroxy-1-(hydroxymethyl)ethyl]-2,4,6-triiodo-5-lactamidoisophthalamide [60166-93-0].
»Iopamidol contains not less than 98.0percent and not more than 101.0percent of iopamidol,calculated on the dried basis.
Packaging and storage— Preserve in well-closed,light-resistant containers.Store at 25,excursions permitted between 15and 30.
Identification—
A:Infrared Absorption á197Kñ.
B: Heat about 500mg in a suitable crucible:violet vapors are evolved.
C: The retention time of the major peak in the chromatogram of the Test solutioncorresponds to that observed in the chromatogram of the System suitability solution,as obtained in the test for Related compounds.
Specific rotation á781Sñ: between -4.6and -5.2(t=20;l=436nm).
Test solution: 400mg 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.
Loss on drying á731ñ— Dry it at 105for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Free aromatic amine— Transfer 500mg to a 25-mLvolumetric flask,and add 20mLof water,heating on a water bath,if necessary,to effect solution.To a second 25-mLvolumetric flask transfer 18.4mLof water and 1.6mLof a Standard solution prepared by dissolving a suitable quantity of USP Iopamidol Related Compound A RSin water and diluting with water to obtain a solution having a concentration of 62.5µg per mL.To a third 25-mLvolumetric flask add 20mLof water to provide a blank.Treat each flask as follows.Place the flasks in an ice bath,protected from light,for 5minutes.[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 1mLof hydrochloric acid,mix,and allow to stand for 5minutes.Add 1mLof sodium nitrite solution (1in 50),mix,and allow to stand for 5minutes.Add 1mLof ammonium sulfamate solution (3in 25),shake,and allow to stand for 5minutes.[Caution—Considerable pressure is produced. ]Add 1mLof N-(1-naphthyl)ethylenediamine dihydrochloride solution (1in 1000),and mix.Remove the flasks from the ice bath,and allow to stand in a water bath at about 25for 10minutes.Dilute with water to volume,mix,and without delay (about 5minutes 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 500nm,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 2.0g to a stoppered,50-mLcentrifuge tube,add sufficient water to dissolve,heating on a water bath,if necessary,to effect solution,and dilute with water to 25mL.Add 5mLof toluene and 5mLof 2Nsulfuric acid,shake well,and centrifuge:the toluene layer shows no red color.
Limit of free iodide— Transfer about 6.0g,accurately weighed,to a suitable container,dissolve in 50mLof water,and add 2.0mLof 0.001Mpotassium iodide.Titrate with 0.001Nsilver 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 mLof 0.001Nsilver nitrate is equivalent to 126.9µg of iodide.Not more than 0.001%is found.
Free acid or alkali— Dissolve 10.0g in 100mLof freshly boiled and cooled water.Using a pHmeter and a glass-calomel electrode system,determine the volume of 0.01Nhydrochloric acid VSor 0.01Nsodium hydroxide VSto bring the pHof the test solution to 7.0:not more than 1.37mLof 0.01Nsodium hydroxide,equivalent to a free acid content of 5mg of hydrochloric acid per 100g,or not more than 0.75mLof 0.01Nhydrochloric acid,equivalent to a free alkali content of 3mg of sodium hydroxide per 100g,is required.
Heavy metals,Method IIá231ñ: 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 Aand Solution Bas directed under Chromatographic system.
System suitability solution— Transfer 10.0mg of USP Iopamidol Related Compound B RSand 10.0mg of USP Iopamidol RSto a 1000-mLvolumetric flask.Dissolve in and dilute with water to volume,and mix.
Test solution— Transfer about 1.0g of Iopamidol,accurately weighed,to a 100-mLvolumetric flask,add water to volume,and mix.
Chromatographic system(see Chromatography á621ñ)— 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 1.5mLper minute.The chromatograph is programmed to provide variable mixtures of Solution Aand Solution B,the percentage of Solution Bbeing 8.0%at the time of injection,and is held at that percentage for 6minutes,then increased linearly to 35.0%at 18minutes,after which it is changed to increase linearly to 92.0%at 30minutes,maintained at that percentage for 4minutes,and decreased linearly to 8.0%at 36minutes,where it is held to the end of the run at 40minutes.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the resolution,R,between iopamidol related compound Band iopamidol is not less than 7.
Procedure— Separately inject equal volumes (about 20µL)of the System suitability solutionand the Test solutioninto 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 riis the peak response for the individual related compound obtained from the Test solution;and rsis the peak response for iopamidol related compound Bobtained from the System suitability solution.The sum of all related compounds does not exceed 0.25%.
Assay— Transfer about 300mg of Iopamidol,accurately weighed,to a glass-stoppered,125-mLconical flask,add 40mLof 1.25Nsodium hydroxide and 1g of powdered zinc,connect the flask to a reflux condenser,and reflux the mixture 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 5mLof glacial acetic acid,and titrate with 0.1Nsilver nitrate VS,determining the endpoint potentiometrically.Each mLof 0.1Nsilver nitrate is equivalent to 25.90mg of C17H22I3N3O8.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1046
Pharmacopeial Forum:Volume No.29(6)Page 1909
Phone Number:1-301-816-8305