Diatrizoate Meglumine and Diatrizoate Sodium Injection
»Diatrizoate Meglumine and Diatrizoate Sodium Injection is a sterile solution of Diatrizoate Meglumine and Diatrizoate Sodium in Water for Injection,or a sterile solution of Diatrizoic Acid in Water for Injection prepared with the aid of Sodium Hydroxide and Meglumine.It contains not less than 95.0percent and not more than 105.0percent of the labeled amounts of diatrizoate meglumine (C11H9I3N2O4·C7H17NO5)and of iodine (I).It may contain small amounts of suitable buffers and of Edetate Calcium Disodium or Edetate Disodium as a stabilizer.Diatrizoate Meglumine and Diatrizoate Sodium Injection intended for intravascular use contains no antimicrobial agents.
Packaging and storage— Preserve either in single-dose containers,preferably of Type Ior Type IIIglass,protected from light or,where intended for administration with a pressure injector through a suitable transfer connection,in similar glass 500-mLor 1000-mLbottles,protected from light.
Labeling— Label containers of Injection intended for intravascular injection,where packaged in single-dose containers,to direct the user to discard any unused portion remaining in the container or,where packaged in bulk bottles to state,“Bulk Container—only for sterile filling of pressure injectors,”to state that it contains no antimicrobial preservatives,and to direct the user to discard any unused portion remaining in the container after 6hours.Indicate also in the labeling of bulk bottles that a pressure injector is to be charged with a dose just prior to administration of the Injection.Label containers of Injection intended for other than intravascular injection to show that the contents are not intended for intravascular injection.
Identification—
A: Dilute a volume of Injection,if necessary,with a 0.8in 1000solution of sodium hydroxide in methanol to obtain a test solution having a concentration of 1mg per mL.The test solution responds to the Thin-layer Chromatographic Identification Test á201ñ,the Standard solution being prepared at a concentration of 1mg of USP Diatrizoic Acid RSper 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: Evaporate a volume of Injection,equivalent to about 500mg of diatrizoate meglumine and diatrizoate sodium,to dryness,and heat the residue so obtained in a suitable crucible:violet vapors are evolved.
Bacterial endotoxins á85ñ— It contains not more than 1.8USP Endotoxin Units per mLfor Injections containing less than 60%of diatrizoate meglumine,and not more than 3.6USP Endotoxin Units for Injections containing 60%or more of diatrizoate meglumine.
pHá791ñ: between 6.0and 7.7.
Free aromatic amine— Transfer an accurately measured volume of Injection,equivalent to about 1g of diatrizoate meglumine and diatrizoate sodium,to a 50-mLvolumetric flask.Dilute with water to 5mL,and add 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.Proceed as directed in the test for Free aromatic amineunder Diatrizoate Meglumine,beginning with “To a third 50-mLvolumetric flask add 5mLof water”.
Iodine and iodide— Transfer an accurately measured volume of Injection,equivalent to about 2.0g of the total of diatrizoate meglumine and diatrizoate sodium,to a 50-mLcentrifuge tube provided with a stopper.Dilute with water to 24mL.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 volume of potassium iodide solution (1in 4000),containing a quantity of iodide corresponding to 0.02%of the weight of diatrizoate meglumine and diatrizoate sodium in the volume of Injection taken is diluted with water to 24mLand substituted for the solution under test (0.02%of iodide).
Heavy metals á231ñ— In a 50-mLcolor-comparison tube,mix a volume of Injection,equivalent to 1.0g of the total of diatrizoate meglumine and diatrizoate sodium,with 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%.
Other requirements— It meets the requirements under Injections á1ñ.
Assay for diatrizoate meglumine— Pipet 5mLof Injection into a 10-mLvolumetric flask,add water to volume,and mix.Determine the angular rotation (see Optical Rotation á781ñ)of the diluted Injection,using a 100-mm tube.Calculate the content,in mg per mL,of C11H9I3N2O4·C7H17NO5in the Injection by the formula:
2000a/6.01,
in which ais the observed angular rotation,in degrees,corrected for the blank,and the factor 6.01is the specific rotation,in degrees,of diatrizoate meglumine.
Assay for iodine— Transfer an accurately measured volume of Injection,equivalent to about 4g of the total of diatrizoate meglumine and diatrizoate sodium,to a 50-mLvolumetric flask,dilute with water to volume,and mix.Pipet 5mLof this solution into 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 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 6.345mg of iodine.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 614
Phone Number:1-301-816-8305