Sulfamethazine

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

Sulfamethazine contains NLT 99.0% and NMT 100.5% of sulfamethazine (C₁₂H₁₄N₄O₂S), calculated on the dried basis.

2 IDENTIFICATION

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

B. Procedure

Sample: 0.10 g of Sulfamethazine

Analysis: To the Sample add 10 mL of water and just sufficient 0.1 N sodium hydroxide (4 mg/mL) to give a faint pink spot on phenolphthalein paper. Add 5 drops of cupric sulfate TS.

Acceptance criteria: A yellow-green precipitate is formed, and it becomes brown on standing.

3 ASSAY

Procedure

Analysis: Proceed as directed in Nitrite Titration 〈451〉.

Calculate the percentage of sulfamethazine (C₁₂H₁₄N₄O₂S) in the portion of Sulfamethazine taken:

Result = V × M × F × (1/W) × 100

V = volume of Titrant consumed by the Sample (mL)

M = actual Titrant concentration, in molarity (mEq/mL)

F = equivalency factor of sulfamethazine, 278.3 mg/mEq

W = weight of the Sample taken (mg)

Acceptance criteria: 99.0%–100.5% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Delete the following:

Selenium 〈291〉:

Sample: 200 mg of Sulfamethazine

Acceptance criteria: NMT 30 ppm (USP 1-Aug-2022)

Ordinary Impurities 〈466〉

Sample solution: Acetone

Standard solution: Acetone

Eluant: Ethyl acetate, methanol, and ammonium hydroxide (17:6:5)

Visualization: 11

5 SPECIFIC TESTS

Melting Range or Temperature 〈741〉: 197°–200°

Acidity

Sample: 3.0 g of Sulfamethazine

Sample solution: Digest the Sample with 150 mL of carbon dioxide-free water at 70° for about 5 min, stirring occasionally to maintain suspension of the Sample. Cool the mixture rapidly in an ice bath to 20 ± 0.5°, with mechanical stirring. Filter immediately, with vacuum, omitting washing of the solid but drying it thoroughly by suction. Use the filtrate.

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant 1: 0.1 N sodium hydroxide VS

Titrant 2: 0.1 M sodium nitrite VS

Endpoint detection: Visual

Analysis 1: To 25.0 mL of the Sample solution add 2 drops of thymolphthalein TS. Titrate with Titrant 1. Record the volume of Titrant 1 consumed (V ).

Analysis 2: To a second 25.0-mL portion of the Sample solution add 10 mL of hydrochloric acid. Cool the mixture to 15°, and proceed as directed in Nitrite Titration 〈451〉. Record the volume of Titrant 2 consumed (V ).

Result = V₁ − V₂

V₁ = volume of Titrant 1 consumed by the Sample solution in Analysis 1 (mL)

V₂ = volume of Titrant 2 consumed by the Sample solution in Analysis 2 (mL)

Acceptance criteria: NMT 0.5 mL

Loss on Drying 〈731〉

Sample: 1 g of Sulfamethazine

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

Clarity and Color of Solution

Sample: 1 g of Sulfamethazine

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

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

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Sulfamethazine RS