Acamprosate Calcium

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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C₁₀H₂₀CaN₂O₈S₂         400.48

1-Propanesulfonic acid, 3-(acetylamino)-, calcium salt (2:1);

Calcium 3-(acetylamino) propane-1-sulfonate CAS RN: 77337-73-6

1 DEFINITION

Acamprosate Calcium contains NLT 98.0% and NMT 102.0% of acamprosate calcium C₁₀H₂₀CaN₂O₈S₂, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K_{(CN 1-MAY-2020)}

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Calcium: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Mobile phase: Add 5.0 mL of triethylamine per 1 L of water and adjust with phosphoric acid to a pH of 4.0.

System suitability solution: 10 mg/mL of USP Acamprosate Calcium RS and 0.005 mg/mL each of USP Acamprosate Related Compound B RS and glacial acetic acid in water. Sonication may be used to aid in dissolution.

Standard solution: 0.3 mg/mL of USP Acamprosate Calcium RS in water. Sonication may be used to aid in dissolution.

Sample solution: 0.3 mg/mL of Acamprosate Calcium in water. Sonication may be used to aid in dissolution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 0.7 mL/min

Injection volume: 20 μL

Run time: NLT 2 times the retention time of the acamprosate peak

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between acetic acid and acamprosate related compound B; NLT 1.3 between acamprosate related compound B and

acamprosate, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of acamprosate calcium (C₁₀H₂₀CaN₂O₈S₂) in the portion of Acamprosate Calcium 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 Acamprosate Calcium RS in the Standard solution (mg/mL)

C_u = concentration of Acamprosate Calcium in the Sample solution (mg/mL)

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

4 IMPURITIES

Change to read:

4.1 Limit of Acamprosate Related Compound A

Solution A: 5 g/L of fluorescamine in acetonitrile. Use within 24 h of preparation.

Buffer: 13.8 g/L of monobasic sodium phosphate prepared as follows. Transfer a suitable amount of monobasic sodium phosphate to a volumetric flask. Dissolve in 90% of the final flask volume of water. Adjust with 10 N sodium hydroxide TS or phosphoric acid to a pH of 6.5. Dilute with water to volume.

Mobile phase: Acetonitrile, methanol, and Buffer (10:10:80)

Diluent: 24.6 g/L of boric acid prepared as follows. Transfer a suitable amount of boric acid to an appropriate volumetric flask. Dissolve in 90% of the final flask volume of water. Adjust with 10 N sodium hydroxide TS to a pH of 10.4. Dilute with water to volume.

Standard stock solution A: 250 μg/mL of USP Acamprosate Related Compound A RS in water

Standard stock solution B: 1 μg/mL of USP Acamprosate Related Compound A RS from Standard stock solution A in Diluent

Standard solution: Transfer 3.0 mL of Standard stock solution B to an appropriate container. Add 0.15 mL of Solution A and shake vigorously for 30 s. Heat in a water bath at 50° for 30 min. Cool under a stream of cold water, centrifuge, and pass the supernatant through a suitable membrane filter.

Sample stock solution A: 20 mg/mL of Acamprosate Calcium in water

Sample stock solution B: 2000 μg/mL of Acamprosate Calcium from Sample stock solution A in Diluent

Sample solution: Transfer 3.0 mL of Sample stock solution B to an appropriate container. Add 0.15 mL of Solution A and shake for 30 s. Heat in a water bath at 50° for 30 min. Cool under a stream of cold water, centrifuge, and pass the supernatant through a suitable membrane filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 261 nm

Column: 4.6-mm × 15-cm; 3- or 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 2 times the retention time of acamprosate related compound A

System suitability

Sample: Standard solution

[Note—The relative retention times for fluorescamine and acamprosate related compound A are about 0.5 and 1.0, respectively. Acamprosate calcium is not detected by this chromatographic system.]

Suitability requirements

Resolution: NLT 2.0 between

uorescamine and acamprosate related compound A

Relative standard deviation: NMT 5.0% for acamprosate related compound A

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of acamprosate related compound A in the portion of Acamprosate Calcium 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 Acamprosate Related Compound A RS (ERR 1-Dec-2018) in the Standard solution (μg/mL)

C_u = concentration of Acamprosate Calcium in the Sample solution (μg/mL)

Acceptance criteria: NMT 0.05%

4.2 Organic Impurities

Mobile phase: Add 5.0 mL of triethylamine per 1 L of water and adjust with phosphoric acid to a pH of 4.0.

System suitability solution: 10 mg/mL of USP Acamprosate Calcium RS and 0.005 mg/mL each of USP Acamprosate Related Compound B RS and glacial acetic acid in water. Sonication may be used to aid in dissolution.

Standard solution: 0.005 mg/mL of USP Acamprosate Calcium RS in water. Sonication may be used to aid in dissolution.

Sample solution: 10 mg/mL of Acamprosate Calcium in water. Sonication may be used to aid in dissolution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 0.7 mL/min

Injection volume: 20 μL

Run time: NLT 6 times the retention time of the acamprosate peak

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention time for acetic acid is 0.7; see Table 1 for the other relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between acetic acid and acamprosate related compound B; NLT 1.3 between acamprosate related compound B and

acamprosate, System suitability solution

Tailing factor: NMT 1.5 for acamprosate, Standard solution

Relative standard deviation: NMT 15.0% for acetic acid, System suitability solution; NMT 5% for acamprosate, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Acamprosate Calcium taken:

Result = (r_u /r_s) × (C_s /C_u) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of acamprosate from the Standard solution

C_s = concentration of USP Acamprosate Calcium RS in the Standard solution (mg/mL)

C_u = concentration of Acamprosate Calcium in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

a Included for identication only. This peak is due to the calcium counterion and hence is not an impurity.

b 3-(N-Methylacetamido)propane-1-sulfonate.

c The sum of acamprosate related compound A from the Limit of Acamprosate Related Compound A test and all impurities from the test for Organic Impurities.

5 SPECIFIC TESTS

5.1 pH 〈791〉

Sample solution: 0.05 g/mL of Acamprosate Calcium in carbon dioxide-free water

Acceptance criteria: 5.5–7.0

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.4%

6 ADDITIONAL REQUIREMENTS

6.1 Packaging and Storage: Store in tight containers.

6.2 USP Reference Standards 〈11〉

USP Acamprosate Calcium RS

USP Acamprosate Related Compound A RS

3-Aminopropane-1-sulfonic acid.

C₃H₉NO₃S    139.17

USP Acamprosate Related Compound B RS

Calcium 3-formamidopropane-1-sulfonate.

C₈H₁₆CaN₂O₈S₂    372.42