Edetate Disodium Compounded Ophthalmic 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

Edetate Disodium Compounded Ophthalmic Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of edetate disodium (C₁₀H₁₄N₂Na₂O₈).

Prepare Edetate Disodium Compounded Ophthalmic Solution 10 mg/mL (1%) to 40 mg/mL (4%) as follows (see Pharmaceutical Compounding—Sterile Preparations 〈797〉).

Add Edetate Disodium Dihydrate and Sodium Chloride to 8 mL of Water for Injection and mix until dissolved. Adjust with Sodium Hydroxide

Solution (1 N) to a pH between 6.1 and 7.1. (ERR 1-Jul-2024) Add suficient Water for Injection to bring to final volume, and mix well. Pass through a sterilizing filter of 0.22-μm pore size into a sterile single-dose ophthalmic dropper container. [Note—Sodium Chloride is added to the formulation to render it isotonic.]

Add Edetate Disodium Dihydrate to 8 mL of Water for Injection and mix until dissolved. Adjust with Sodium Hydroxide Solution (1 N) to a pH between 6.1 and 7.1. (ERR 1-Jul-2024) Add su ficient Water for Injection to bring to final volume, and mix well. Pass through a sterilizing filter of 0.22-μm pore size into a sterile single-dose ophthalmic dropper container.

2 ASSAY

Procedure

Solution A: Dissolve 10 mg of cupric sulfate in 1 L of water. Add 15 mL of tetrabutyl ammonium hydroxide and 20 mL of tetrahydrofuran.

Adjust with phosphoric acid to a pH of 4.

Mobile phase: Methanol and Solution A (15:85)

Standard solution: 0.2 mg/mL of edetate disodium prepared from USP Edetate Disodium RS in water

Sample solution: Transfer a volume of Ophthalmic Solution equivalent to 20 mg of edetate disodium into a 100-mL volumetric flask, and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm × 25-cm; 5-μm packing L96

Column temperature: 40°

Flow rate: 2 mL/min

Injection volume: 5 μL

System suitability

Sample: Standard solution

[Note—Edetate disodium may covalently bind the column packing material and may cause retention time to range between 15 and 20 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of edetate disodium (C₁₀H₁₄N₂Na₂O₈) in the portion of Ophthalmic Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak response from the Sample solution

r_S= peak response from the Standard solution

C_S = concentration of USP Edetate Disodium RS in the Standard solution (mg/mL)

C_U = nominal concentration of edetate disodium in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 6.1–7.1

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in a sterile plastic ophthalmic single-unit container for use in one patient only. Store in a refrigerator or at controlled room temperature.

Beyond-Use Date: In the absence of passing a sterility test, the beyond-use dates in Pharmaceutical Compounding—Sterile Preparations 〈797〉 apply. After successful completion of sterility testing, NMT 60 days after the day on which it was compounded when stored at controlled room temperature or in a refrigerator.

Labeling: Label it to state the Beyond-Use Date. Label it to indicate that it is for ophthalmic use only.

USP Reference Standards 〈11〉

USP Edetate Disodium RS