Sulfasalazine Tablets

General Notices

Action and use

Sulfonamide aminosalicylate; treatment of ulcerative colitis.

Definition

Sulfasalazine Tablets contain Sulfasalazine.

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

Content of sulfasalazine, C18H14N4O5S

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 16 mg of Sulfasalazine with 100 mL of 0.1m sodium hydroxide until dispersed and filter. Dilute 5 mL of the filtrate to 100 mL with a mixture of 7 volumes of water and 2 volumes of 0.1m acetic acid. Record the light absorbances in the range 220 nm to 400 nm, Appendix II B. The absorbances at all wavelengths in the range are similar to those of a solution prepared from sulfasalazine BPCRS in the same manner.
B. In the test for Related substances, the principal peak in the chromatogram obtained with solution (2) corresponds to that in the chromatogram obtained with solution (4).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of a phosphate buffer prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate and 1.66 g of sodium hydroxide in sufficient water to produce 1000 mL and adjusting the pH to 7.5 with 5m sodium hydroxide if necessary, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, diluted with the dissolution medium, if necessary, to produce a solution containing 0.005% w/v of Sulfasalazine, at the maximum at 406 nm, Appendix II B using dissolution medium in the reference cell.
(2) Measure the absorbance of a 0.005% w/v solution of sulfasalazine BPCRS in dissolution medium in the reference cell.
determination of content

Calculate the total content of sulfasalazine, C18H14N4O5S, in the medium from the absorbances obtained and using the declared content of C18H14N4O5S, in sulfasalazine BPCRS.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 0.1 g of Sulfasalazine with 100 mL of 0.1m ammonia for 30 minutes, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 100 volumes with 0.1m ammonia.
(3) 0.001% w/v of sulfasalazine derivative for resolution EPCRS in solution (2).
(4) 0.001% w/v of sulfasalazine BPCRS in 0.1m ammonia.
(5) Dilute 1 volume of solution (2) to 20 volumes with 0.1m ammonia.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil 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 320 nm.
(f) Inject 20 µL of each solution.

Mobile phase A0.013% w/v of sodium dihydrogen orthophosphate and 0.25% w/v of sodium acetate adjusted to pH 4.8 with glacial acetic acid.

Mobile phase B1 volume of mobile phase A and 4 volumes of methanol.

When the chromatograms are recorded in the prescribed conditions, the retention times relative to sulfasalazine (retention time about 24 minutes) are: salicylic acid (impurity H), about 0.16; impurity I, about 0.28; impurity C, about 0.80; impurity F, about 0.85; impurity G, about 1.39; impurity E, about 1.63; impurity B, about 1.85; impurity D, about 1.90 and impurity A, about 2.00.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to sulfasalazine and sulfasalazine derivative for resolution is at least 3.

limits

In the chromatogram obtained with solution (1):

the area of any peaks corresponding to impurities A, B, C, D, E, F, G and I are not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1% of each);

the area of any other secondary peak is not greater than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%);

the sum of the areas of any secondary peaks is not greater than four times the area of the principal peak in the chromatogram obtained with solution (2) (4%).

Disregard any peak with a retention time shorter than 6 minutes (corresponding to salicylic acid and sulfapyridine) and any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.05%).

Salicylic acid and sulfapyridine

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 0.1 g of Sulfasalazine with 100 mL of 0.1m ammonia for 30 minutes, centrifuge and use the supernatant liquid.
(2) 0.05% w/v of salicylic acid and 0.05% w/v of sulfapyridine BPCRS in 0.1m ammonia and dilute 1 volume of this solution to 50 volumes with 0.1m ammonia.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic 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 300 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for 10 minutes.
mobile phase

30 volumes of mobile phase B described in the test for Related substances and 70 volumes of mobile phase A described in the test for Related substances.

When the chromatogram is recorded using the prescribed conditions the retention time of salicylic acid is about 6 minutes and that of sulfapyridine is about 7 minutes.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (2), the resolution between the peaks due to salicylic acid and sulfapyridine is at least 2.

limits

In the chromatogram obtained with solution (1), the area of any peak corresponding to salicylic acid or sulfapyridine is not greater than 0.5 times the area of the corresponding peaks in the chromatogram obtained with solution (2) (0.5% of each).

Assay

Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.15 g of Sulfasalazine with about 50 mL of 0.1m sodium hydroxide, add sufficient of the same solvent to produce 100 mL, filter and discard the first 20 mL of filtrate. Dilute 5 mL of the filtrate with 750 mL of water, add 20 mL of 0.1m acetic acid, mix and add sufficient water to produce 1000 mL. Measure the absorbance of this solution at the maximum at 359 nm, Appendix II B. Calculate the content of C18H14N4O5S in the tablets from the absorbance of a standard solution prepared in the same manner using 0.15 g of sulfasalazine BPCRS and using the declared content of C18H14N4O5S in sulfasalazine BPCRS.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed under Sulfasalazine.