Sulfasalazine

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

Sulfasalazine contains NLT 97.0% and NMT 101.5% of C₁₈H₁₄N₄O₅S, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy : 197K (CN 1-M  -2020)

B. PROCEDURE

Standard solution: Use the Standard solution, prepared as directed in the Assay. Sample solution: Use the Sample solution, prepared as directed in the Assay.

Acceptance criteria: The visible absorption spectrum of the Sample solution corresponds to that of the Standard solution, as obtained from the Assay.

3 ASSAY

PROCEDURE

Sample stock solution: 1.5 mg/mL of Sulfasalazine in 0.1 N sodium hydroxide

Sample solution: Transfer 5.0 mL of the Sample stock solution to a 1000-mL volumetric flask containing 750 mL of water, mix, add 20.0 mL of

0.1 N acetic acid, and dilute with water to volume.

Standard solution: 7.5 µg/mL of USP Sulfasalazine RS in the same medium as the Sample solution Spectrometric conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV-Vis

Analytical wavelength: Maximum at about 359 nm Blank: Water

Analysis

Samples: Standard solution, Sample solution, and Blank

Concomitantly determine the absorbances of the Samples. Calculate the percentage of C₁₈H₁₄N₄O₅S in the portion of Sulfasalazine taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Sulfasalazine RS in the Standard solution (µg/mL)

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

Acceptance criteria: 97.0%–101.5% on the dried basis

4 IMPURITIES

4.1 INORGANIC IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.5%

CHLORIDE AND SULFATE, Chloride 〈221〉

Analysis: Digest 2.0 g of Sulfasalazine with 100 mL of water at 70° for 5 min. Cool immediately to room temperature, and filter. Transfer a 25-mL portion of the filtrate to a 50-mL beaker (retain the remainder of this filtrate for the Sulfate test). Add 1 mL of nitric acid, mix, and allow to stand for 5 min. Pass through a fine texture, retentive filter paper (Whatman No. 42, or equivalent).

Acceptance criteria: The filtrate shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (0.014%).

CHLORIDE AND SULFATE, Sulfate〈221〉

Analysis: Transfer a 25-mL portion of the filtrate from the Chloride test to a 50-mL beaker. Add 1 mL of 3 N hydrochloric acid, mix, and allow to stand for 5 min. Pass through a fine texture, retentive filter paper (Whatman No. 42, or equivalent).

Acceptance criteria: The filtrate shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (0.04%).

4.2 ORGANIC IMPURITIES

PROCEDURE

Standard stock solution: 10 mg/mL of USP Sulfasalazine RS in a mixture of alcohol and 2 M ammonium hydroxide (4:1)

Standard solutions: Dilute aliquots of the Standard stock solution stepwise with the same medium to obtain solutions having concentrations of 200, 150, 100, and 20 µg/mL, corresponding to 2.0%, 1.5%, 1.0%, and 0.2%, respectively (Standard solutions A, B, C, and D).

Sample solution: 10 mg/mL of Sulfasalazine in a mixture of alcohol and 2 M ammonium hydroxide (4:1)

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Chloroform, acetone, and formic acid (12:6:1)

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the chapter. Allow the spots to dry, and develop the chromatogram in an unequilibrated chamber until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, dry with the aid of a current of hot air, and examine the plate under short-wavelength UV light.

Acceptance criteria: The R value of the principal spot of the Sample solution corresponds to that of the Standard solution. No spots, other

than the principal spot, in the chromatogram of the Sample solution are larger or more intense than the principal spot of Standard solution A (2%), and the sum of the intensities of any secondary spots detected does not exceed 4%.

5 SPECIFIC TESTS

LOSS ON DRYING 〈731〉: Dry a sample at 105° for 2 h: it loses NMT 1.0% of its weight.

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS 〈11〉

USP Sulfasalazine RS