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 95.0 percent and not more than 105.0 percent 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 I or Type III glass, protected from light or, where intended for administration with a pressure injector through a suitable transfer connection, in similar glass 500-mL or 1000-mL bottles, protected from light. Injection packaged for other than intravascular use may be packaged in 100-mL multiple-dose containers, preferably of Type I or Type III glass, 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 6 hours. 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.
USP Reference standards 11
USP Diatrizoic Acid RS Click to View Structure
USP Diatrizoic Acid Related Compound A RS Click to View Structure
5-Acetamido-3-amino-2,4,6-triiodobenzoic acid.
    C9H7I3N2O3    571.88
USP Endotoxin RS
Identification—
A: Dilute a volume of Injection, if necessary, with a 0.8 in 1000 solution of sodium hydroxide in methanol to obtain a test solution having a concentration of 1 mg per mL. The test solution responds to the Thin-layer Chromatographic Identification Test 201, the Standard solution being prepared at a concentration of 1 mg of USP Diatrizoic Acid RS per mL in a 0.8 in 1000 solution of sodium hydroxide in methanol, the solvent mixture being a mixture of chloroform, methanol, and ammonium hydroxide (20:10:2), and short-wavelength UV light being used to locate the spots.
B: Evaporate a volume of Injection, equivalent to about 500 mg of diatrizoate meglumine, to dryness, and heat the residue so obtained in a suitable crucible: violet vapors are evolved.
Bacterial endotoxins 85 It contains not more than 1.1 USP Endotoxin Units per mL for Injections containing less than 50% of diatrizoate meglumine, and less than 5.0 USP Endotoxin Units per mL for Injections containing 50% or more of diatrizoate meglumine.
pH 791: between 6.0 and 7.7.
Iodine and iodide— Dilute a volume of Injection, equivalent to 2.0 g of diatrizoate meglumine, with 24 mL of water in a 50-mL centrifuge tube provided with a stopper. Add 5 mL of toluene and 5 mL of 2 N sulfuric acid, shake, and centrifuge: the toluene layer shows no red color. Add 1 mL of sodium nitrite solution (1 in 50), shake, and centrifuge: any red color in the toluene layer is not darker than that obtained when a volume of potassium iodide solution (1 in 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 24 mL and substituted for the solution under test (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 diatrizoate meglumine, 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 in the test for Heavy metals under Diatrizoate Meglumine: the limit is 0.002%.
Free aromatic amine— Transfer a volume of Injection, accurately measured and equivalent to 1 g of diatrizoate meglumine, to a glass-stoppered, 50-mL volumetric flask. Dilute with water to 5 mL, and add 10 mL of 0.1 N sodium hydroxide. Into a second 50-mL volumetric flask pipet a known volume of a Standard solution prepared by dissolving a suitable quantity of USP Diatrizoic Acid Related Compound A RS in 0.1 N sodium hydroxide. Use 0.2 mL of 0.1 N sodium hydroxide for each 5.0 mg of Standard, and dilute with water to obtain a known concentration of 500 µg 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 5 mL, and add 10 mL of 0.1 N sodium hydroxide. Proceed as directed in the test for Free aromatic amine under Diatrizoate Meglumine, beginning with “To a third 50-mL volumetric flask add 5 mL of water”.
Meglumine content— Determine the angular rotation (see Optical Rotation 781) 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 a is 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 1.
Assay— Pipet a volume of Injection, or a suitable dilution of it, equivalent to about 600 mg of diatrizoate meglumine, into a glass-stoppered, 125-mL conical flask, add 30 mL of 1.25 N sodium hydroxide and 500 mg of powdered zinc, connect the flask to a reflux condenser, and reflux the mixture for 1 hour. 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 filter and the flask thoroughly, adding the rinsings to the filtrate. Add 5 mL of glacial acetic acid and 1 mL of tetrabromophenolphthalein ethyl ester TS, and titrate with 0.05 N silver nitrate VS until the yellow precipitate just turns green. Each mL of 0.05 N silver nitrate is equivalent to 13.49 mg of C11H9I3N2O4·C7H17NO5.
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