Disulfiram Tablets

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

Disulfiram Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of disulfiram (C₁₀H₂₀N₂S₄).

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K _{▲(CN 1-May-2020)}

Standard: USP Disulfiram RS

Sample: A portion of powdered Tablets

Acceptance criteria: Meet the requirements

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 TS to a pH of 7.0.

Mobile phase: Methanol and Buffer (70:30)

Standard stock solution: 1 mg/mL of USP Disulfiram RS in alcohol. Use this solution within 5 days.

Standard solution: 0.02 mg/mL of USP Disulfiram RS from the Standard stock solution diluted with Mobile phase. Use this solution within 1 day.

Sample stock solution: Nominally 1 mg/mL of disulfiram from Tablets prepared as follows. Powder NLT 20 Tablets and transfer a suitable portion of the powder to an appropriate volumetric flask. Add 70% of the flask volume of alcohol and swirl, sonicate for about 5 min, and shake by mechanical means for 30 min or until dissolved. Dilute with alcohol to volume and pass through a suitable filter. Use the filtrate. Use this solution within 5 days.

Sample solution: Nominally 0.02 mg/mL of disulfiram from Sample stock solution in Mobile phase. Use this solution within 1 day.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Column: 3.9-mm x 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 1.5 times the retention time of disulfiram

3.2.1 System suitability

Sample: Standard solution

3.2.2 Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

3.2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of disulfiram (C₁₀H₂₀N₂S₄) in the portion of Tablets 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 (mg/mL)

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISINTEGRATION (701)

Time: 15 min, the use of disks being omitted

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

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

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and Buffer (50:50)

System suitability solution: 0.05 mg/mL of USP Disulfiram RS and 0.01 mg/mL of sulfiram in Diluent. Use this solution within 1 day.

Standard stock solution: 0.25 mg/mL of USP Disulfiram RS in methanol. Use this solution within 1 day.

Standard solution: 0.002 mg/mL of USP Disulfiram RS from Standard stock solution in Diluent. Use this solution within 1 day.

Sensitivity solution: 0.001 mg/mL of USP Disulfiram RS from Standard solution in Diluent. Use this solution within 1 day.

Sample stock solution: Nominally 2.5 mg/mL of disulfiram from NLT 5 Tablets in methanol. Store at 4° and use it within 2 h.

Sample solution: Nominally 1 mg/mL of disulfiram from Sample stock solution in Diluent. Store at 4° and use it within 2 h.

5.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 3.9-mm x 15-cm; 5-µm, 300 Å packing 11

Autosampler temperature: 4°

Flow rate: 1 mL/min

Injection volume: 15 µL

5.1.2 System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[NOTE-See Table 2 for relative retention times.]

5.1.3 Suitability requirements

Resolution: NLT 8.0 between sulfiram and disulfiram, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

5.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

                Result = (r_U/r_S) x (C_S/C_U) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of disulfiram from the Standard solution s

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

^a 1,1,3,3-Tetraethylthiourea.

^b Diethylthiocarbamic thioanhydride.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Disulfiram RS