Diatrizoate Meglumine and Diatrizoate Sodium Solution

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Diatrizoate Meglumine and Diatrizoate Sodium Solution is a solution of Diatrizoic Acid in Purified Water prepared with the aid of Meglumine and Sodium Hydroxide. It can also be a solution of Diatrizoate Meglumine and Diatrizoate Sodium in Purified Water. It contains NLT 95.0% and NMT 105.0% of the labeled amounts of diatrizoate meglumine (C₁₁H₉I₃N₂O₄ · C₇H₁₇NO₅) and of iodine (I). It may contain small amounts of suitable buffers, Edetate Disodium, and flavoring agents.

2 IDENTIFICATION

2.1 A. Thin-Layer Chromatographic Identification Test 〈201〉

Diluent: Sodium hydroxide in methanol (0.8 in 1000)

Standard solution: 1 mg/mL of USP Diatrizoic Acid RS in Diluent

Sample solution: 1 mg/mL from a volume of Solution, in Diluent

Developing solvent system: Methanol, chloroform, and ammonium hydroxide (10:20:2)

Analysis

• Samples: Sample solution and Standard solution
• Locate the spots using short-wavelength UV light.

Acceptance criteria: Meets the requirements

2.2 B.

Sample solution: Nominally 500 mg of diatrizoate meglumine and diatrizoate sodium from a volume of Solution

Analysis: Evaporate the Sample solution to dryness and heat the residue so obtained in a crucible.

Acceptance criteria: Violet vapors are evolved.

3 ASSAY

3.1 Diatrizoate Meglumine

Sample stock solution: 6 mg/mL of diatrizoate meglumine and diatrizoate sodium prepared as follows. Pipet a volume of Solution equivalent to 1.5 g of diatrizoate meglumine and diatrizoate sodium to a 250-mL volumetric flask, and dilute with water to volume.

Sample solution: Pipet 10 mL of the Sample stock solution into a glass-stoppered 250-mL flask. Add 4 mL of 2 N sulfuric acid and 20 mL of sodium metaperiodate solution (1 in 200). Insert the stopper, and set aside in the dark for 1 h. Add 50 mL of water, mix, and add 10 mL of potassium iodide TS. Insert the stopper quickly and mix by swirling for 20 s.

Titrimetric system

• Mode: Direct titration
• Titrant: 0.1 N sodium thiosulfate VS
• Endpoint detection: Visual

Analysis: Immediately titrate the Sample solution with Titrant, using 3 mL of starch TS. Perform a blank determination, and make any necessary correction. Each milliliter of 0.1 N sodium thiosulfate is equivalent to 10.11 mg of diatrizoate meglumine (C₁₁H₉I₃N₂O₄ · C₇H₁₇NO₅).

Acceptance criteria: 95.0%–105.0%

3.2 Iodine

Sample stock solution: 0.08 g/mL of the total of diatrizoate meglumine and diatrizoate sodium prepared as follows. Transfer an accurately measured volume of Solution, equivalent to 4 g of the total of diatrizoate meglumine and diatrizoate sodium, to a 50-mL volumetric flask, and dilute with water to volume, and mix.

Sample solution: Pipet 5 mL of Sample stock solution 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 h. 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 filter thoroughly, adding the rinsings to the filtrate. Add 5 mL of glacial acetic acid and 1 mL of tetrabromophenolphthalein ethyl ester TS.

Titrimetric system

• Mode: Direct titration
• Titrant: 0.05 N silver nitrate VS
• Endpoint detection: Visual

Analysis: Titrate the Sample solution with Titrant until the yellow precipitate just turns green. Each milliliter of 0.05 N silver nitrate is equivalent to 6.345 mg of iodine (I).

Acceptance criteria: 95.0%–105.0%

4 SPECIFIC TESTS

4.1 pH 〈791〉: 6.0–7.6

4.2 Iodine and Iodide

Solution A: Sodium nitrite solution (1 in 50)

Standard stock solution: Potassium iodide solution (1 in 4000)

Standard solution: Combine 2.0 mL of Standard stock solution and 22 mL of water in a stoppered 50-mL centrifuge tube.

Sample solution: Dilute a volume of Solution, equivalent to 2 g of diatrizoate meglumine and diatrizoate sodium, with water to 24 mL in a stoppered 50-mL centrifuge tube. Shake to promote dissolution.

Analysis

Samples: Standard solution and Sample solution

To each of the Samples, 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 Solution A, shake, and centrifuge.

Acceptance criteria: Any red color in the toluene layer of the Sample solution is not darker than the toluene layer of the Standard solution.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Labeling: Label the container to indicate that the contents are not intended for parenteral use.

USP Reference Standards 〈11〉

USP Diatrizoic Acid RS