Sodium Succinate

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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NaOOC-CH₂CH₂-COONa (C₄H₄Na₂O₄) 162.05

Anhydrous disodium 1,4-butanedioate;

Anhydrous butanedioic acid disodium salt CAS RN^®: 150-90-3.

NaOOC-CH₂CH₂-COONa·6H₂O (C₄H₄Na₂O₄·6H₂O) 270.14

Disodium 1,4-butanedioate hexahydrate;

Butanedioic acid disodium salt hexahydrate CAS RN^®: 6106-21-4.

1 DEFINITION

Sodium Succinate, when dried at 120° for 2 h, contains NLT 98.0% and NMT 102.0% of disodium succinate (C₄H₄Na₂O₄).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A OR 197K (CN 1-MAY-2020) Dry the Anhydrous Sodium Succinate or

Sodium Succinate Hexahydrate sample at 120° for 2 h before use.

B. CHROMATOGRAPHIC IDENTITY

Analysis: Proceed as directed in the Assay.

C. SODIUM

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Solution A: Dissolve 6.8 g of monobasic potassium phosphate in 2 L of water. Adjust with phosphoric acid to a pH of 2.3. Pass under vacuum through an HNWP (nylon hydrophilic) membrane filter of 0.45-µm pore size. This is a 25 mM potassium phosphate buffer with a pH of 2.3.

Mobile phase: Add 100 mL of methanol to 1900 mL of Solution A and mix well. Sonicate for 30 min and cool to room temperature.

Diluent: Add 10 mL of phosphoric acid to 1 L of water and mix well. This is a 1% phosphoric acid solution.

System suitability solution: 3.0 mg/mL of USP Anhydrous Sodium Succinate RS and 2.2 µg/mL of USP Fumaric Acid RS in Diluent

Standard solution: 3.0 mg/mL of USP Anhydrous Sodium Succinate RS in Diluent

Sample solution: 3.0 mg/mL of Anhydrous Sodium Succinate or Sodium Succinate Hexahydrate in Diluent. Dry Anhydrous Sodium Succinate or Sodium Succinate Hexahydrate at 120° for 2 h before use.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 204 nm

Column: 4.6-mm x 15-cm; 3-µm packing L1

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: 10 min

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for succinic acid and fumaric acid are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 2.0 between succinic acid and fumaric acid, System suitability solution

Tailing factor: 0.8-2.0, Standard solution

Relative standard deviation: NMT 0.5%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sodium succinate (C₄H₄Na₂O₄) in the portion of sample taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Anhydrous Sodium Succinate RS in the Standard solution (mg/mL)

C_U = concentration of Anhydrous Sodium Succinate or Sodium Succinate Hexahydrate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0%

4 IMPURITIES

4.1 LIMIT OF SODIUM ACETATE, SODIUM MALEATE, AND SODIUM FUMARATE

Solution A, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Acetic acid stock solution: Transfer 37.5 mg of USP Glacial Acetic Acid RS to a 25-mL volumetric flask that contains 10 mL of Diluent. Dissolve and dilute with Diluent to volume. Transfer 1.0 mL of this solution to a 10-mL volumetric flask and dilute with Diluent to volume. This solution is equivalent to 200 µg/mL of sodium acetate in Diluent.

Maleic acid stock solution: Transfer 36.5 mg of USP Maleic Acid RS to a 50-mL volumetric flask. Dissolve and dilute with Diluent to volume. Transfer 1.0 mL of this solution to a 10-mL volumetric flask and dilute with Diluent to volume. This solution is equivalent to 100 µg/mL of sodium maleate in Diluent.

Fumaric acid stock solution: Transfer 36.5 mg of USP Fumaric Acid RS to a 50-mL volumetric flask. Dissolve and dilute with Diluent to volume. Transfer 1.0 mL of this solution to a 10-mL volumetric flask and dilute with Diluent to volume. This solution is equivalent to 100 µg/mL of sodium fumarate in Diluent.

System suitability solution: 10 mg/mL of USP Anhydrous Sodium Succinate RS, 15 µg/mL of USP Glacial Acetic Acid RS, and 7.3 µg/mL each of USP Maleic Acid RS and USP Fumaric Acid RS in Diluent

Standard solution: Transfer 1 mL each of Acetic acid stock solution, Maleic acid stock solution, and Fumaric acid stock solution to a 10-mL volumetric flask and dilute with Diluent to volume.

Sample solution: 10 mg/mL of Anhydrous Sodium Succinate or Sodium Succinate Hexahydrate in Diluent

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for acetic acid, maleic acid, succinic acid, and fumaric acid are 0.7, 0.8, 1.0, and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.5 between acetic acid and maleic acid; NLT 2.0 between succinic acid and fumaric acid, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Based on the Standard solution, identify the peaks of acetic acid, maleic acid, and fumaric acid. Compare peak areas of acetic acid, maleic acid, and fumaric acid in the Standard solution and the Sample solution.

Acceptance criteria

Sodium acetate: The peak area of acetic acid in the Sample solution is NMT the peak area of acetic acid in the Standard solution, corresponding to NMT 0.2% of sodium acetate in Sodium Succinate.

Sodium maleate: The peak area of maleic acid in the Sample solution is NMT the peak area of maleic acid in the Standard solution, corresponding to NMT 0.1% of sodium maleate in Sodium Succinate.

Sodium fumarate: The peak area of fumaric acid in the Sample solution is NMT the peak area of fumaric acid in the Standard solution, corresponding to NMT 0.1% of sodium fumarate in Sodium Succinate.

4.2 LIMIT OF SULFATE

Standard solution: 0.4 mL of 0.005 mol/L sulfuric acid

Sample solution: Dissolve 1.0 g of Anhydrous Sodium Succinate or Sodium Succinate Hexahydrate in 30 mL of water and neutralize with a diluted hydrochloric acid (1 in 40).

Analysis: Proceed as directed in Chloride and Sulfate (221), Sulfate.

Acceptance criteria: NMT 0.019% as SO₄

5 SPECIFIC TESTS

5.1 ACIDITY AND ALKALINITY

Sample solution: Dissolve 1.0 g of Anhydrous Sodium Succinate or Sodium Succinate Hexahydrate in carbon dioxide-free water and dilute with water to 20 mL.

Analysis: Proceed as directed in pH (791).

Acceptance criteria: 7.0-9.0

5.2 LOSS ON DRYING (731)

Analysis: Proceed as directed in Loss on Drying (731). Dry at 120° for 2 h.

Acceptance criteria

Anhydrous Sodium Succinate: NMT 2.0%

Sodium Succinate Hexahydrate: 37.0%-41.0%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers. Store at room temperature.

6.2 LABELING

Label it to state, as part of the official title, anhydrous or hexahydrate for sodium succinate.

6.3 USP REFERENCE STANDARDS (11)

USP Anhydrous Sodium Succinate RS

USP Fumaric Acid RS

USP Glacial Acetic Acid RS

USP Maleic Acid RS