Benzethonium Chloride Concentrate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Benzethonium Chloride Concentrate contains NLT 94.0% and NMT 106.0% of the labeled amount of benzethonium chloride (C₂₇H₄₂CINO₂).

2 IDENTIFICATION

2.1 A.

Sample: Evaporate a volume of the Concentrate, equivalent to 200 mg of benzethonium chloride, on a steam bath.

Analysis: To the residue add 2 mL of alcohol, 0.5 mL of 2 N nitric acid, and 1 mL of silver nitrate TS.

Acceptance criteria: A white precipitate, which is insoluble in 2 N nitric acid but soluble in 6 N ammonium hydroxide, is formed.

2.2 B.

Sample: Evaporate a volume of the Concentrate, equivalent to 200 mg of benzethonium chloride, on a steam bath.

Analysis: To the residue add 0.1 g of potassium nitrate, and heat on a steam bath for 3 min. Cautiously dilute the solution with water to 10 mL, add 0.5 g of granulated zinc, and warm the mixture for 10 min. Cool. Add 0.2 g of sodium nitrite to 1 mL of the clear liquid, and add this mixture to 20 mg of naphthol dipotassium disulfonate or naphthol disodium disulfonate in 1 mL of ammonium hydroxide.

Acceptance criteria: The solution turns orange-red, and a brown precipitate may be formed.

3 ASSAY

3.1 PROCEDURE

Sample solution: Equivalent to 200 mg of benzethonium chloride from a volume of Concentrate, in a glass-stoppered flask

Analysis: Add 0.4 mL of bromophenol blue solution (1 in 2000), 10 mL of chloroform, and 1 mL of 1 N sodium hydroxide. Titrate with 0.02 M sodium tetraphenylboron VS until the blue color disappears from the chloroform layer. Add the last portions of the sodium tetraphenylboron solution dropwise, agitating vigorously after each addition. Each mL of 0.02 M sodium tetraphenylboron is equivalent to 8.962 mg of benzethonium chloride (C₂₇H₄₂CINO₂).

Acceptance criteria: 94.0%-106.0% of the labeled amount of benzethonium chloride

4 IMPURITIES

4.1 LIMIT OF NITRITES

Sample: One drop of Concentrate on a spot plate

Analysis: To the Sample add one drop each of glacial acetic acid, sulfanilic acid in acetic acid solution (1 in 100), and 1-naphthylamine-acetic acid solution (prepared by boiling 30 mg of 1-naphthylamine in 70 mL of water, decanting the colorless solution from the blue-violet residue, and mixing with 30 mL of glacial acetic acid).

Acceptance criteria: No red color develops in the resulting solution within 10 min.

5 SPECIFIC TESTS

5.1 OXIDIZING SUBSTANCES

Sample: 5 mL

Analysis: To the Sample add 0.5 mL of potassium iodide TS and a few drops of 3 N hydrochloric acid.

Acceptance criteria: The solution does not acquire a yellow color.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at room temperature.

LABELING: The label states that this article is not intended for direct administration to humans or animals.