Sulfamethizole

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

Sulfamethizole contains NLT 98.0% and NMT 101.0% of sulfamethizole, calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M

B.

Sample: 0.1 g

Analysis: Add 5 mL of 3 N hydrochloric acid to the Sample, and boil gently for 5 min. Cool in an ice bath, then add 4 mL of 1% sodium nitrite solution, add water to make 10 mL, and place the mixture in an ice bath for 10 min. To 5 mL of the cooled mixture add a solution of 50 mg of 2-naphthol in 2 mL of 10% sodium hydroxide solution.

Acceptance criteria: An orange-red precipitate is formed, and it darkens on standing.

C.

Sample: 20 mg

Analysis: Suspend the Sample in 5 mL of water, add dropwise 1 N sodium hydroxide until dissolved, then add 2 or 3 drops of cupric sulfate TS.

Acceptance criteria: A light green precipitate is formed, and it does not change on standing.

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

3 ASSAY

Procedure

Mobile phase: Methanol, glacial acetic acid, and water (30:1:69)

Standard stock solution: 0.4 mg/mL of USP Sulfamethizole RS in methanol

Standard solution: 8 μg/mL of USP Sulfamethizole RS from the Standard stock solution in Mobile phase

Sample stock solution: 0.4 mg/mL of Sulfamethizole in methanol

Sample solution: 8 μg/mL of Sulfamethizole from the Sample stock solution in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; 10-μm packing L1

Flow rate: 1 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 2000 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sulfamethizole in the portion of Sulfamethizole 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 Sulfamethizole RS in the Standard solution (μg/mL)

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

Acceptance criteria: 98.0%–101.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Chloride and Sulfate 〈221〉, Chloride

Sample solution: A 25.0-mL portion of the filtrate prepared in the test for Acidity

Acceptance criteria: 0.014%; shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid

Chloride and Sulfate 〈221〉, Sulfate

Sample solution: A 25.0-mL portion of the filtrate prepared in the test for Acidity

Acceptance criteria: 0.04%; shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid

Delete the following:

Selenium 〈291〉: NMT 0.003% (USP 1-May-2022)

Ordinary Impurities 〈466〉

Standard solution: Methanol

Sample solution: Methanol

Eluant: Acetone

Visualization: 1

Acceptance criteria: Meets the requirements

5 SPECIFIC TESTS

Melting Range or Temperature 〈741〉: 208°–212°

Acidity

Sample: 2.0 g

Analysis: Digest the Sample with 100 mL of water at 70° for 5 min, cool immediately to about 20°, and filter. To 25.0 mL of the filtrate add 2 drops of phenolphthalein TS, and titrate with 0.10 N sodium hydroxide. Save the remainder of the filtrate for the tests for Chloride and Sulfate.

Acceptance criteria: NMT 0.50 mL is required for neutralization.

Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

Clarity and Color of Solution

Sample: 1.0 g

Analysis: Dissolve the Sample in 20 mL of water and 5 mL of 1 N sodium hydroxide.

Acceptance criteria: The solution is clear and not more than pale yellow.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.

USP Reference Standards 〈11〉

USP Sulfamethizole RS