Iothalamate Meglumine and Iothalamate Sodium Injection
»Iothalamate Meglumine and Iothalamate Sodium Injection is a sterile solution of Iothalamic Acid in Water for Injection,prepared with the aid of Meglumine and Sodium Hydroxide.It contains not less than 95.0percent and not more than 105.0percent of the labeled amounts of iothalamate meglumine (C11H9I3N2O4·C7H17NO5)and iothalamate sodium (C11H8I3N2NaO4).It may contain small amounts of suitable buffers and of Edetate Calcium Disodium or Edetate Disodium as a stabilizer.Iothalamate Meglumine and Iothalamate Sodium Injection intended for intravascular use contains no antimicrobial agents.
Packaging and storage— Preserve in single-dose containers,preferably of Type Iglass,protected from light.
Labeling— Label containers of Injection intended for intravascular injection to direct the user to discard any unused portion remaining in the container.Label containers of Injection intended for other than intravascular injection to show that the contents are not intended for intravascular injection.
Identification— Dilute 3mLof Injection with water to 100mL,add an excess of 3Nhydrochloric acid,mix,and filter.Wash the precipitate of iothalamic acid so obtained with four 10-mLportions of water,and dry at 105for 4hours:the dried iothalamic acid so obtained responds to the following tests.
A: The IRabsorption spectrum of a potassium bromide dispersion of it exhibits maxima only at the same wavelengths as that of a similar preparation of USP Iothalamic Acid RS.
B: Heat about 500mg in a suitable crucible:violet vapors are evolved.
Bacterial endotoxins á85ñ— It contains not more than 3.35USP Endotoxin Units per mL.
pHá791ñ: between 6.5and 7.7.
Free aromatic amine— Dilute a suitable volume of Injection with water to yield a solution containing 100mg of the total of iothalamate meglumine and iothalamate sodium per mL.Pipet 5mLof this solution into a 50-mLvolumetric flask,and add 10mLof water.Proceed as directed in the test for Free aromatic amineunder Iothalamic Acid,beginning with “In another flask place 15mLof water.The absorbance of the solution from the Injection is not greater than that of the Standard solution (0.05%).
Iodine and iodide— Dilute a volume of Injection,equivalent to 2g of the total of iothalamate meglumine and iothalamate sodium,with 20mLof water in a 50-mLbeaker,and proceed as directed for Procedurein the test for Iodine under Iothalamic Acid,beginning with “add 5mLof 2Nsulfuric acid.”The limit of Iodine and Iodideis 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 iothalamate meglumine and iothalamate sodium,with 5mLof 1Nsodium hydroxide,dilute with water to 40mL,and mix.Using this as the Test preparation,proceed as directed for Heavy metalsunder Diatrizoate Meglumine:the limit is 0.002%.
Other requirements— It meets the requirements under Injections á1ñ.
Assay for iothalamate 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 10-cm cell and a suitable polarimeter.Calculate the quantity,in mg per mL,of iothalamate meglumine in the Injection taken 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 iothalamate meglumine.
Assay for iothalamate sodium— Transfer an accurately measured volume of Injection,equivalent to about 4g of iothalamate meglumine and iothalamate sodium,to a 250-mLvolumetric flask,dilute with water to volume,and mix.Pipet 25mLof this solution into a glass-stoppered,125-mLconical flask,add 12mLof 5Nsodium 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 40mLof 2Nsulfuric acid,and titrate immediately with 0.05Nsilver nitrate VS,determining the end–point potentiometrically,using silver–calomel electrodes and an agar–potassium nitrate salt bridge.Calculate the volume,in mL,consumed by the iothalamate meglumine in the portion of solution taken,using the value found in the Assay for iothalamate meglumine.Each mLof 0.05Nsilver nitrate is equivalent to 13.49mg of C11H9I3N2O4·C7H17NO5.Subtract this volume from the total volume of 0.05Nsilver nitrate consumed.Use the resulting volume to calculate the amount,in mg per mL,of iothalamate sodium in the Injection.Each mLof 0.05Nsilver nitrate is equivalent to 10.60mg of C11H8I3N2NaO4.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1052
Phone Number:1-301-816-8305