Disulfiram

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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C₁₀H₂₀N₂S₄              296.54

Thioperoxydicarbonic diamide [(H₂N)C(S)]₂S₂ tetraethyl-;

Bis(diethylthiocarbamoyl) disulfide CAS RN^®: 97-77-8; UNII: TR3MLJ1UAI.

1 DEFINITION

Disulfiram contains NLT 98.0% and NMT 102.0% of C₁₀H₂₀N₂S₄

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

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

3 ASSAY

3.1 PROCEDURE

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with 45% potassium hydroxide solution to a pH of 7.0.

Mobile phase: Methanol and Buffer (7:3)

Standard stock solution: 1 mg/mL of USP Disulfiram RS in alcohol. [NOTE-Discard this solution after 5 days.]

Standard solution: 0.02 mg/mL of USP Disulfiram RS from the Standard stock solution diluted with Mobile phase. [NOTE-Prepare the Standard solution fresh daily.]

Sample stock solution: Transfer 50 mg of Disulfiram to a 50-mL volumetric flask, add 40 mL of alcohol, sonicate for 5 min to completely dissolve, cool, and dilute with alcohol to volume. [NOTE-Discard this solution after 5 days.] Sample solution: 0.02 mg/mL of Disulfiram from the Sample stock solution diluted with Mobile phase. [NOTE-Prepare the Sample solution fresh daily.]

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4-mm x 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 μL

3.1.2 System suitability

Sample: Standard solution

3.1.3 Suitability requirements

Column efficiency: NLT 1800 theoretical plates

Tailing factor: NMT 2

Relative standard deviation: NMT 2.0%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₀H₂₀N₂S₄ in the portion of Disulfiram taken:

                Result = (r_U/r_S) x (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 Disulfiram RS in the Standard solution (µg/mL)

C_U = concentration of Disulfiram in the Sample solution (µg/mL)

Acceptance criteria: 98.0%-102.0%

4 IMPURITIES

INORGANIC IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

Change to read:

Selenium (291), Procedures, Procedure 1 _{▲(CN 1-Jun-2023)}: 30 ppm

[NOTE-Perform this test only if selenium is a known inorganic process impurity.]

5 SPECIFIC TESTS

MELTING RANGE OR TEMPERATURE, Class I(741): 69°-72°

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

USP REFERENCE STANDARDS (11)

USP Disulfiram RS