Disulfiram Tablets

General Notices

Action and use

Aldehyde dehyrogenase inhibitor; treatment of alcoholism.

Definition

Disulfiram Tablets contain Disulfiram.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of disulfiram, C10H20N2S4

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing 0.2 g of Disulfiram by shaking with 5 mL of dichloromethane and filter. Evaporate the filtrate to dryness and dry the residue at 40° at a pressure not exceeding 0.7 kPa. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of disulfiram (RS 111).
B. In the test for Related substances, the principal spot in the chromatogram obtained with solution (2) corresponds to that in the chromatogram obtained with solution (3).
C. Extract a quantity of the powdered tablets containing 0.3 g of disulfiram with ethanol (96%), filter and evaporate the filtrate to dryness. Dissolve 50 mg of the residue in 5 mL of ethanol (96%) and add 1 mL of potassium cyanide solution. A yellow colour is produced which becomes green and then darkens to bluish green.

TESTS

Diethyldithiocarbamate

Shake a quantity of the powdered tablets containing 0.1 g of Disulfiram with 10 mL of chloroform and filter. Add 10 mL of 0.1m sodium hydroxide to the filtrate, shake, discard the chloroform layer and wash the aqueous layer with three 10 mL quantities of chloroform. To the aqueous layer add 0.25 mL of a 0.4% w/v solution of copper(ii) sulfate and 2 mL of dichloromethane, shake and allow to separate. The lower layer is not more intensely coloured than a standard prepared at the same time and in the same manner by adding 10 mL of 0.1m sodium hydroxide to 0.2 mL of a freshly prepared 0.0075% w/v solution of sodium diethyldithiocarbamate and beginning at the words ‘add 0.25 mL of a 0.4% w/v solution of copper(II) sulfate ...’ (0.01%, calculated as the acid).

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel GF254 as the coating substance and a mixture of 30 volumes of butyl acetate and 70 volumes of n-hexane as the mobile phase. Apply separately to the plate 10 µL of each of the following solutions. For solution (1) extract a quantity of the powdered tablets containing 0.50 g of Disulfiram with 20 mL of ethyl acetate and filter. For solution (2) dilute 1 volume of solution (1) to 100 volumes with ethyl acetate. Solution (3) contains 0.025% w/v of disulfiram BPCRS in ethyl acetate. Solution (4) contains 0.050% w/v of monosulfiram BPCRS in ethyl acetate. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). In the chromatogram obtained with solution (1) any spot corresponding to monosulfiram is not more intense than the spot in the chromatogram obtained with solution (4) (2%) and any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (1%).

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing 0.4 g of Disulfiram add 75 mL of methanol and shake for 30 minutes. Add sufficient methanol to produce 100 mL, filter and dilute 5 mL of the filtrate to 100 mL with methanol. To 5 mL of this solution add sufficient of a 0.1% w/v solution of copper(ii) chloride in methanol to produce 25 mL, mix and allow to stand for 1 hour. Measure the absorbance of the resulting solution at the maximum at 400 nm, Appendix II B, using in the reference cell a solution prepared by diluting 5 mL of methanol to 25 mL with the copper(II) chloride solution. Repeat the operation using 5 mL of a 0.020% w/v solution of disulfiram BPCRS in methanol, beginning at the words ‘add sufficient of a 0.1% w/v solution of copper(ii) chloride…’. Calculate the content of C10H20N2S4 from the absorbances obtained and using the declared content of C10H20N2S4 in disulfiram BPCRS.

Storage

Disulfiram Tablets should be protected from light.