Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Folic acid synthesis inhibitor; treatment of leprosy.
DEFINITION
Dapsone Tablets contain Dapsone.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of dapsone, C12H12N2O2S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 0.1 g of Dapsone with 20 mL of acetone, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of dapsone ( RS 084).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of 0.1M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes, withdraw a sample of the medium and filter. Dilute with the dissolution medium, if necessary, to produce a solution expected to contain 0.0056% w/v of Dapsone.
(2) Dilute 1 volume of a solution containing 2.22% w/v of dapsone BPCRS in acetonitrile to 20 volumes with the dissolution medium, dilute 1 volume of this solution to 20 volumes with the dissolution medium.
(3) 0.0125% w/v each of dapsone BPCRS and 4-(4-aminobenzene-1-sulfonyl)phenol (impurity A).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography with embedded polar groups (3.5 µm (Symmetry Shield RP18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
25 volumes of acetonitrile and 75 volumes of 0.05M potassium dihydrogen orthophosphate previously adjusted to pH 3.0 with orthophosphoric acid.
When the chromatograms are recorded under the prescribed conditions, the retention time of dapsone is about 7 minutes.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to dapsone and impurity A is at least 1.5.
DETERMINATION OF CONTENT
Calculate the total content of dapsone, C12H12N2O2S, in the medium from the chromatograms obtained and using the declared content of C12H12N2O2S in dapsone BPCRS.
LIMITS
The amount of dapsone released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in solution A.
Solution A Equal volumes of acetonitrile and water.
(1) Shake a quantity of powdered tablets containing 40 mg of Dapsone in 30 mL. Dilute to 100 mL and filter (a 0.45-μm nylon syringe filter is suitable).
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) Dilute 1 volume of a solution containing 0.004% w/v each of dapsone BPCRS, 4-(4-aminobenzene-1-sulfonyl)phenol (impurity A), 4-(benzenesulfonyl)aniline (impurity B) and 4,4′-[oxybis[(4,1-phenylene)sulfonyl]]dianiline (impurity C) to 10 volumes.
(4) Dilute 1 volume of solution (2) to 5 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Discovery C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
Mobile phase A water.
Mobile phase B acetonitrile.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-10 | 75 | 25 | isocratic |
| 10-20 | 75→50 | 25→50 | linear gradient |
| 20-35 | 50 | 50 | isocratic |
| 35-36 | 50→75 | 50→25 | linear gradient |
| 36-50 | 75 | 25 | re-equilibration |
SYSTEM SUITABILITY
The test is not valid unless:
in the chromatogram obtained with solution (3), the resolution between the peaks due to dapsone and impurity A is at least 2.0;
in the chromatogram obtained with solution (4), the signal-to-noise ratio of the peak due to dapsone is at least 30.
CALCULATION OF IMPURITIES
For each impurity, use the concentration of dapsone in solution (2).
For the reporting threshold, use the concentration of dapsone in solution (4). For peak identification, use solution (3).
Dapsone retention time: about 7 minutes.
Relative retention: impurity A, about 1.1; impurity B, about 2.5 and impurity C, about 3.5.
Correction factors: impurity A, multiply by 1.9; impurity B, multiply by 2.7 and impurity C, multiply by 1.7.
LIMITS
— impurities A and B: not more than 0.4% of each;
— impurity C: not more than 0.3%;
— unspecified impurities: for each impurity, not more than 0.2%;
— total impurities: not more than 2.0%;
— reporting threshold: 0.1%.
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in acetonitrile.
(1) Mix, with the aid of ultrasound and frequent swirling, a quantity of powdered tablets containing 50 mg of Dapsone with 70 mL. Dilute to produce 100 mL and filter (a 0.45-μm nylon syringe filter is suitable).
(2) 0.05% w/v of dapsone BPCRS.
(3) 0.05% w/v each of dapsone BPCRS and 4-(4-aminobenzene-1-sulfonyl)phenol (impurity A).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with an injection volume of 5 µL.
SYSTEM SUITABILITY
The Assay is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to dapsone and impurity A is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of C12H12N2O2S in the tablets from the chromatograms obtained and using the declared content of C12H12N2O2S in dapsone BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B and C listed under Dapsone.
