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 95.0 percent and not more than 105.0 percent 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 I glass, 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 3 mL of Injection with water to 100 mL, add an excess of 3 N hydrochloric acid, mix, and filter. Wash the precipitate of iothalamic acid so obtained with four 10-mL portions of water, and dry at 105 for 4 hours: the dried iothalamic acid so obtained responds to the following tests.
A: The IR absorption 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 500 mg in a suitable crucible: violet vapors are evolved.
Bacterial endotoxins 85— It contains not more than 3.35 USP Endotoxin Units per mL.
pH 791: between 6.5 and 7.7.
Free aromatic amine— Dilute a suitable volume of Injection with water to yield a solution containing 100 mg of the total of iothalamate meglumine and iothalamate sodium per mL. Pipet 5 mL of this solution into a 50-mL volumetric flask, and add 10 mL of water. Proceed as directed in the test for Free aromatic amine under Iothalamic Acid, beginning with “In another flask place 15 mL of 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 2 g of the total of iothalamate meglumine and iothalamate sodium, with 20 mL of water in a 50-mL beaker, and proceed as directed for Procedure in the test for Iodine under Iothalamic Acid, beginning with “add 5 mL of 2 N sulfuric acid.” The limit of Iodine and Iodide is 0.02% of iodide.
Heavy metals 231— In a 50-mL color-comparison tube, mix a volume of Injection, equivalent to 1.0 g of the total of iothalamate meglumine and iothalamate sodium, with 5 mL of 1 N sodium hydroxide, dilute with water to 40 mL, and mix. Using this as the Test preparation, proceed as directed for Heavy metals under Diatrizoate Meglumine: the limit is 0.002%.
Other requirements— It meets the requirements under Injections 1.
Assay for iothalamate meglumine— Pipet 5 mL of Injection into a 10-mL volumetric flask, add water to volume, and mix. Determine the angular rotation (see Optical Rotation 781) 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 a is the observed angular rotation, in degrees, corrected for the blank; and the factor 6.01 is the specific rotation, in degrees, of iothalamate meglumine.
Assay for iothalamate sodium— Transfer an accurately measured volume of Injection, equivalent to about 4 g of iothalamate meglumine and iothalamate sodium, to a 250-mL volumetric flask, dilute with water to volume, and mix. Pipet 25 mL of this solution into a glass-stoppered, 125-mL conical flask, add 12 mL of 5 N sodium hydroxide and 1 g of powdered zinc, connect the flask to a reflux condenser, and reflux the mixture for 30 minutes. Cool the flask to room temperature, rinse the condenser with 20 mL of 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 40 mL of 2 N sulfuric acid, and titrate immediately with 0.05 N silver 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 mL of 0.05 N silver nitrate is equivalent to 13.49 mg of C11H9I3N2O4·C7H17NO5. Subtract this volume from the total volume of 0.05 N silver nitrate consumed. Use the resulting volume to calculate the amount, in mg per mL, of iothalamate sodium in the Injection. Each mL of 0.05 N silver nitrate is equivalent to 10.60 mg of C11H8I3N2NaO4.
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Topic/Question Contact Expert Committee
Monograph Ian DeVeau, Ph.D.
Director, Veterinary Drugs and Radiopharmaceuticals
1-301-816-8178		 (RMI05) Radiopharmaceuticals and Medical Imaging Agents 05
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
85 Radhakrishna S Tirumalai, Ph.D.
Senior Scientist
1-301-816-8339		 (MSA05) Microbiology and Sterility Assurance
USP32–NF27 Page 2675