Diatrizoate Meglumine Injection
»Diatrizoate Meglumine Injection is a sterile solution of Diatrizoate Meglumine in Water for Injection,or a sterile solution of Diatrizoic Acid in Water for Injection prepared with the aid of Meglumine.It contains not less than 95.0percent and not more than 105.0percent of the labeled amount of diatrizoate meglumine (C11H9I3N2O4·C7H17NO5).It may contain small amounts of suitable buffers and of Edetate Calcium Disodium or Edetate Disodium as a stabilizer.Diatrizoate Meglumine Injection intended for intravascular use contains no antimicrobial agents.
Packaging and storage— Preserve Injection intended for intravascular injection 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.Injection packaged for other than intravascular use may be packaged in 100-mLmultiple-dose containers,preferably of Type Ior Type IIIglass,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,to dryness,and heat the residue so obtained in a suitable crucible:violet vapors are evolved.
Bacterial endotoxins á85ñ— It contains not more than 1.1USP Endotoxin Units per mLfor Injections containing less than 50%of diatrizoate meglumine,and less than 5.0USP Endotoxin Units per mLfor Injections containing 50%or more of diatrizoate meglumine.
pHá791ñ: between 6.0and 7.7.
Iodine and iodide— Dilute a volume of Injection,equivalent to 2.0g of diatrizoate meglumine,with 24mLof water in a 50-mLcentrifuge tube provided with a stopper.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 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 diatrizoate meglumine,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%.
Free aromatic amine— Transfer a volume of Injection,accurately measured and equivalent to 1g of diatrizoate meglumine,to a glass-stoppered,50-mLvolumetric flask.Dilute with water to 5mL,and add 10mLof 0.1Nsodium hydroxide.Into a second 50-mLvolumetric flask pipet a known volume of 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.The volume of Standard solution used contains a quantity of free aromatic amine corresponding to 0.05%of the weight of diatrizoate meglumine in the volume of Injection taken.Dilute with water to 5mL,and add 10mLof 0.1Nsodium hydroxide.Proceed as directed in the test for Free aromatic amineunder Diatrizoate Meglumine,beginning with “To a third 50-mLvolumetric flask add 5mLof water”.
Meglumine content— Determine the angular rotation (see Optical Rotation á781ñ)of the Injection,using a 10-cm cell and a suitable polarimeter.Calculate the content,in mg per mL,of meglumine in the Injection by the formula:
1000a/24.9,
in which ais the observed angular rotation,in degrees,corrected for the blank,and the factor,24.9,is the average specific rotation,in degrees,of meglumine.The meglumine content is between 22.9%and 25.3%of the labeled amount of diatrizoate meglumine.
Other requirements— It meets the requirements under Injections á1ñ.
Assay— Pipet a volume of Injection,or a suitable dilution of it,equivalent to about 600mg of diatrizoate meglumine,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 filter and the flask 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
Phone Number:1-301-816-8305