Silver Sulfadiazine

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

Silver Sulfadiazine contains NLT 98.0% and NMT 102.0% of silver sulfadiazine (C₁₀H₉AgN₄O₂S), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. IDENTIFICATION TESTS—GENERAL 〈191〉 , Chemical Identification Tests, Silver

Sample: 1 g in 15 mL of ammonium hy droxide and 15 mL of water in a 50-mL volumetric flask. Dilute with water to volume, and mix. Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Solution A: 0.77 g/L of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 5.2 ± 0.1.

Solution B: Methanol

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile, ammonium hydroxide, and water (5:6:90)

Standard solution: 0.05 mg/mL of USP Silver Sulfadiazine RS in Diluent. Sonicate, if necessary, to dissolve.

Sample solution: 0.05 mg/mL of Silver Sulfadiazine in Diluent

3.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 275 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

3.1.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of silver sulfadiazine (C₁₀H₉AgN₄O₂S) in the portion of Silver Sulfadiazine taken:

Result = (r_U/r_S) × (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 Silver Sulfadiazine RS in the Standard solution (mg/mL)

C_U = concentration of Silver Sulfadiazine in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 OTHER COMPONENTS

4.1 CONTENT OF SILVER

Sample solution: Add 500 mg to 150 mL of water and 50 mL of nitric acid, and stir for 15 min.

Titrimetric system (See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N potassium thiocy anate VS or 0.1 N ammonium thiocy anate VS Endpoint detection: Potentiometric

Analysis: Titrate the Sample solution with Titrant using a silver-based indicator electrode and a double-junction reference electrode. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N potassium thiocy anate VS or 0.1 N ammonium thiocy anate VS is equivalent to 10.79 mg of silver.

Acceptance criteria: 29.3%–30.5% of silver is found.

5 IMPURITIES

5.1 LIMIT OF NITRATE

Standard solution: 200 µg/mL of nitrate from potassium nitrate

Sample solution: Add 30.0 mL of water to 2 g of Silver Sulfadiazine, stir for 20 min, and pass through a suitable, nitrate-free filter.

5.1.1 Instrumental conditions

Mode: UV-Vis

Analytical wavelength: 408 nm Blank: Deionized water

5.1.2 Analysis

Samples: Standard solution, Sample solution, and Blank

Pipet 3 mL of the Sample solution and Blank into separate test tubes. Pipet 1 mL of the Standard solution and 2 mL of water into a third test tube. Cool the three test tubes in an ice bath. Slowly add 7.0 mL of cold chromotropic acid solution, prepared by dissolving 50 mg of chromotropic acid in 100 mL of cold sulfuric acid, to each test tube, while swirling, and allow the test tubes to remain in the ice bath for 3 min after the addition of the chromotropic acid solution. Remove the test tubes from the ice bath, and allow to stand for 30 min. Concomitantly determine the absorbances of the Sample solution and the Standard solution with a suitable spectrophotometer, against the Blank.

Calculate the percentage of nitrate content in the portion of Silver Sulfadiazine 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 nitrate in the Standard solution (µg/mL)

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

Acceptance criteria: NMT 0.1%

5.2 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1.0 mg/mL of USP Silver Sulfadiazine RS and 0.001 mg/mL each of USP Sulfanilic Acid RS, USP Sulfanilamide RS, and sulfaguanidine in Diluent

Standard solution: 0.001 mg/mL of USP Silver Sulfadiazine RS in Diluent Sample solution: 1.0 mg/mL of Silver Sulfadiazine in Diluent

5.2.1 System suitability

Samples: System suitability solution and Standard solution

[NOTE—The relative retention times for sulfaguanidine and sulfanilamide are about 0.65 and 0.71, respectively.]

Suitability requirements

Resolution: NLT 2.0 between sulfaguanidine and sulfanilamide, System suitability solution

Relative standard deviation: NMT 5.0% for the sulfadiazine peak, Standard solution

5.2.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Silver Sulfadiazine taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of silver sulfadiazine from the Standard solution

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

C_U = concentration of Silver Sulfadiazine in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any impurity peaks less than 0.05%.

Table 2

^a 4-Amino-N-carbamimidoylbenzenesulfonamide.

^b These are controlled using the limit for individual unspecified impurities.

^c Pyrimidin-2-amine.

^d 4-Amino-N-2-pyrimidinyl-benzenesulfonamide.

^e N-{4-[N-(Pyrimidin-2-yl)sulfamoyl]phenyl}acetamide.

^f This compound is a specified unknown impurity. No information is available about the chemical structure or chemical name for this impurity.

6 SPECIFIC TESTS

LOSS ON DRYING 〈731〉

Analysis: Dry at 105° for 1 h.

Acceptance criteria: NMT 0.5%

7 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS 〈11〉

USP Silver Sulfadiazine RS USP Sulfanilamide RS

4-Aminobenzenesulfonamide. C₆H₈N₂O₂S    172.20

USP Sulfanilic Acid RS

4-Aminobenzenesulfonic acid. C₆H₇NO₃S    173.19