Diatrizoate Meglumine
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C11H9I3N2O4·C7H17NO5 809.13

Benzoic acid,3,5-bis(acetylamino)-2,4,6-triiodo-,compd.with 1-deoxy-1-(methylamino)-D-glucitol (1:1).
1-Deoxy-1-(methylamino)-D-glucitol 3,5-diacetamido-2,4,6-triiodobenzoate (salt) [131-49-7].
»Diatrizoate Meglumine contains not less than 98.0percent and not more than 102.0percent of C11H9I3N2O4·C7H17NO5,calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.Store at 25,excursions permitted between 15and 30.
Identification—
A: It responds to the Thin-Layer Chromatographic Identification Test á201ñ,the test solution and the Standard solution of USP Diatrizoic Acid RSbeing prepared at a concentration of 1mg per mLin a 0.8in 1000solution of sodium hydroxide in methanol,the solvent mixture being a mixture of chloroform,methanol,and ammonium hydroxide (20:10:2),and short-wavelength UVlight being used to locate the spots.
B: Heat about 500mg in a suitable crucible:violet vapors are evolved.
Specific rotation á781Sñ: between -5.65and -6.37.
Test solution: 100mg per mL,in water.
Loss on drying á731ñ— Dry it at 105for 4hours:it loses not more than 1.0%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Iodine and iodide—
Test preparation— Transfer 2.0g to a 50-mLcentrifuge tube provided with a stopper,dilute with water to 24mL,and shake to dissolve.
Procedure— Add 5mLof toluene and 5mLof 2Nsulfuric acid,shake,and centrifuge:the toluene layer shows no red color.Add 1mLof sodium nitrite solution (1in 50),shake,and centrifuge:any red color in the toluene layer is not darker than that obtained when a mixture of 2.0mLof potassium iodide solution (1in 4000)and 22mLof water is substituted for the solution under test (0.02%of iodide).
Heavy metals á231ñ—
Standard preparation— Transfer 2.0mLof Standard Lead Solution(20µg of Pb)to a 50-mLcolor-comparison tube,add 5mLof 1Nsodium hydroxide,dilute with water to 40mL,and mix.
Test preparation— Dissolve 1.0g of Diatrizoate Meglumine in 20mLof water and 5mLof 1Nsodium hydroxide,transfer the solution to a 50-mLcolor-comparison tube,dilute with water to 40mL,and mix.
Procedure— To each of the tubes containing the Standard preparationand the Test preparationadd 10mLof sodium sulfide TS,mix,allow to stand for 5minutes,and view downward over a white surface:the color of the solution from the Test preparationis not darker than that of the solution from the Standard preparation(0.002%).
Free aromatic amine— Transfer 1.0g to a 50-mLvolumetric flask,and add 5mLof water and 10mLof 0.1Nsodium hydroxide.To a second 50-mLvolumetric flask transfer 4mLof water,10mLof 0.1Nsodium hydroxide,and 1.0mLof a Standard solution prepared by dissolving a suitable quantity of USP Diatrizoic Acid Related Compound A RSin 0.1Nsodium hydroxide.Use 0.2mLof 0.1Nsodium hydroxide for each 5.0mg of Standard,and dilute with water to obtain a known concentration of 500µg per mL.To a third 50-mLvolumetric flask add 5mLof water and 10mLof 0.1Nsodium hydroxide to provide a blank.
Treat each flask as follows.Add 25mLof methyl sulfoxide,insert the stopper,and mix by swirling gently.Chill in an ice bath in the dark for 5minutes.[NOTE—In conducting the following steps,keep the flasks in the ice bath and in the dark as much as possible until all the reagents have been added.]Add slowly 2mLof hydrochloric acid,mix,and allow to stand for 5minutes.Add 2mLof sodium nitrite solution (1in 50),mix,and allow to stand for 5minutes.Add 1mLof sulfamic acid solution (2in 25),shake,and allow to stand for 5minutes.[Caution—Considerable pressure is produced. ]Add 2mLof a 1in 1000solution of N-(1-naphthyl)ethylenediamine dihydrochloride in dilute propylene glycol (7in 10),and mix.
Remove the flasks from the ice bath and from storage in the dark,and allow to stand in a water bath at 22to 25for 10minutes.Shake gently and occasionally during this period,releasing the pressure by loosening the stopper.Dilute with water to volume,and mix.
Within 5minutes from the time of diluting the solutions in all three flasks to 50mL,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 465nm,with a suitable spectrophotometer,versus the prepared blank.The absorbance of the solution from the Diatrizoate Meglumine is not greater than that of the Standard solution (0.05%).
Assay— Transfer about 400mg of Diatrizoate Meglumine,accurately weighed,to a glass-stoppered,125-mLconical flask,add 30mLof 1.25Nsodium hydroxide and 500mg of powdered zinc,connect the flask to a reflux condenser,and reflux the mixture for 1hour.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 1mLof tetrabromophenolphthalein ethyl ester TS,and titrate with 0.05Nsilver nitrate VSuntil the yellow precipitate just turns green.Each mLof 0.05Nsilver nitrate is equivalent to 13.49mg of C11H9I3N2O4·C7H17NO5.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 613
Pharmacopeial Forum:Volume No.30(3)Page 832
Phone Number:1-301-816-8305