Edetate Calcium Disodium

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

Edetate Calcium Disodium contains NLT 98.0% and NMT 102.0% of edetate calcium disodium (C₁₀H₁₂CaN₂Na₂O₈), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

B. Procedure

Sample: 2 g

Analysis: Dissolve the Sample in 10 mL of water, add 6 mL of lead (II) nitrate solution (33 in 1000), shake, and add 3 mL of potassium iodide TS: no yellow precipitate is formed. Make this solution alkaline by the addition of diluted ammonia solution (7 in 50), and add 3 mL of ammonium oxalate TS.

Acceptance criteria: A white precipitate is formed.

C. Procedure

Sample: 0.5 g

Analysis: Dissolve 0.5 g in 10 mL of water, and add 10 mL of potassium pyroantimonate TS.

Acceptance criteria: A white, crystalline precipitate is formed. The formation of the precipitate is accelerated by rubbing the inside wall of the test tube with a glass rod.

3 ASSAY

Procedure

Sample: 500 mg of Edetate Calcium Disodium

Analysis: Transfer the Sample into a 200-mL volumetric flask. Dissolve in and dilute with water to volume, and mix. Pipet 20 mL of this solution to 80 mL of water, and adjust with diluted nitric acid to a pH of 2–3. Add two drops of xylenol orange TS, and titrate with 0.01 M Bismuth nitrate VS until the color of the solution changes from yellow to red. Each mL of 0.01 M bismuth nitrate VS is equivalent to 3.743 mg of edetate calcium disodium (C₁₀H₁₂CaN₂Na₂O₈).

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Chloride and Sulfate, Chloride〈221〉

Sample solution: To 0.70 g of Edetate Calcium Disodium add 20 mL of water and 30 mL of diluted nitric acid. Allow to stand for 30 min, and filter. To 10 mL of the filtrate add water to make 50 mL.

Control solution: Prepare with 0.40 mL of 0.01 M hydrochloric acid VS.

Analysis: Proceed as directed in the chapter.

Acceptance criteria: NMT 0.10%

Organic Impurities

Procedure 1: Disodium Edetate

Sample: 1.00 g of Edetate Calcium Disodium

Analysis: Dissolve the Sample in 50 mL of water. Add 5 mL of ammonia–ammonium chloride buffer TS, and 40 mg of eriochrome black T–sodium chloride indicator. Titrate with 0.01 M magnesium chloride VS until the color of the solution changes from blue to red-violet.

Acceptance criteria: NMT 3.0 mL of 0.01 M magnesium chloride VS is consumed (NMT 1.0%).

Procedure 2: Limit of Nitrilotriacetic Acid

Mobile phase: Add 10 mL of 1.0 M tetrabutylammonium hydroxide in methanol to 200 mL of water, and adjust with 1 M phosphoric acid to a pH of 7.5 ± 0.1. Transfer the solution to a 1000-mL volumetric flask, add 90 mL of methanol, dilute with water to volume, pass through a filter of 0.5-μm or finer pore size, and degas.

Cupric nitrate solution: 10 mg/mL of cupric nitrate [Cu(NO ) ] in water

Standard stock solution: Transfer 100 mg of nitrilotriacetic acid to a 10-mL volumetric flask, add 0.5 mL of ammonium hydroxide, and mix.

Dilute with water to volume, and mix.

Standard solution: Transfer 1.0 g of Edetate Calcium Disodium to a 100-mL volumetric flask, add 100 μL of Standard stock solution, dilute with Cupric nitrate solution to volume, and mix. Sonicate, if necessary, to achieve complete solution.

System suitability solution: Transfer 10 mg of Edetate Calcium Disodium to a 100-mL volumetric flask, add 100 μL of Standard stock solution, dilute with Cupric nitrate solution to volume, and mix. Sonicate, if necessary, to dissolve.

Sample solution: 10 mg/mL of Edetate Calcium Disodium in Cupric nitrate solution. Sonicate, if necessary, to achieve complete solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; packing L7

Flow rate: 2 mL/min

Injection volume: 50 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for nitrilotriacetic acid, copper, and edetate are about 0.35, 0.65, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3 between nitrilotriacetic acid and copper, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Measure the responses for the major peaks.

Acceptance criteria: The peak response of nitrilotriacetic acid from the Sample solution does not exceed the difference between the

nitrilotriacetic acid peak responses obtained from the Standard solution and the Sample solution (0.1%).

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: A solution (1 in 5)

Acceptance criteria: 6.5–8.0

Water Determination, Method I〈921〉

Sample: 0.2 g

Acceptance criteria: 5.0%–13.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. No storage requirements specified.

USP Reference Standards 〈11〉

USP Edetate Calcium Disodium RS