Benzethonium Chloride Tincture

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

Benzethonium Chloride Tincture contains, in each 100 mL, NLT 190 mg and NMT 210 mg of benzethonium chloride (C₂₇H₄₂CINO₂).

Prepare Benzethonium Chloride Tincture 2 mg/mL as follows.

Dissolve the Benzethonium Chloride in a mixture of Alcohol and Acetone. Add sufficient Purified Water to make 1000 mL. [NOTE-Benzethonium Chloride Tincture may be colored by the addition of any suitable color or combination of colors certified by the FDA for use in drugs.]

2 IDENTIFICATION

2.1 A. PROCEDURE

Sample: 50 mL

Analysis: To the residue obtained by evaporating the Sample on a steam bath, 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. PROCEDURE

Sample: 50 mL

Analysis: Evaporate the Sample on a steam bath.

Acceptance criteria: The residue obtained forms precipitates with 2 N nitric acid and with mercuric chloride TS, both of which dissolve upon the addition of alcohol.

3 ASSAY

3.1 PROCEDURE

Sample: 50 mL

Analysis: Transfer the Sample to a 150-mL beaker, and add, with continuous stirring, 10 mL of 25 mg/mL of sodium tetraphenylboron solution. Cover, and allow to stand for 16 h. Decant the supernatant into a tared sintered-glass crucible, applying vacuum filtration. Suspend the precipitate in 20 mL of water. Transfer the precipitate to the crucible, washing well with water. Dry the precipitate and the crucible at 105° for 1 h, cool, and weigh. The weight of the precipitate so obtained, multiplied by 0.6122, represents its equivalent of benzethonium chloride (C₂₇H₄₂CINO₂).

Acceptance criteria: 190-210 mg

4 OTHER COMPONENTS

4.1 ALCOHOL AND ACETONE CONTENT

Standard solution A (alcohol low standard solution): Add 5.0 mL of methanol and 11.0 mL of dehydrated alcohol to a 100-mL volumetric flask, and dilute with water to volume.

Standard solution B (alcohol high standard solution): Add 5.0 mL of methanol and 14.0 mL of dehydrated alcohol to a 100-mL volumetric flask, and dilute with water to volume.

Standard solution C (acetone low standard solution): Add 5.0 mL of methanol and 1.7 mL of acetone to a 100-mL volumetric flask, and dilute with water to volume.

Standard solution D (acetone high standard solution): Add 5.0 mL of methanol and 2.2 mL of acetone to a 100-mL volumetric flask, and dilute with water to volume.

Sample solution: Transfer 20 mL of Tincture to a 100-mL volumetric flask, add 5.0 mL of methanol as the internal standard, and dilute with water to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 120-cm x 4-mm packed with a suitable type of support, such as 80- to 100-mesh S3

Carrier gas: Dry helium

Temperature

Injector port: 240°

Detector block: 240°

Column: 120°

Flow rate: 90 mL/min

Injection size: 0.8 µL

Analysis

Samples: Standard solutions A, B, C, and D, and Sample solution

From the respective chromatograms obtained as described previously, calculate the ratios of peak areas for alcohol to internal standard and for acetone to internal standard.

Calculate the percentage of alcohol and of acetone in the portion of Tincture taken:

Result = [A(Y - Z) + B(Z - X)]/(Y - X)

A = percentage of alcohol, or of acetone, in Standard solution A and Standard solution C, respectively

Y = ratio of the alcohol peak areas, or the acetone peak areas, to the internal standard peak areas for Standard solution B and Standard solution D, respectively

Z = ratio of the alcohol peak areas, or the acetone peak areas, to the internal standard peak areas for the Sample solution

B = percentage of alcohol, or of acetone, in Standard solution B and Standard solution D, respectively

X = ratio of the alcohol peak areas, or the acetone peak areas, to the internal standard peak areas for Standard solution A and Standard solution C, respectively

Acceptance criteria

Alcohol (C₂H₅OH): 62.0%-68.0%

Acetone (C₃H₆O): 9.0%-11.0%

5 SPECIFIC TESTS

SPECIFIC GRAVITY (841): 0.868-0.876

6 ADDITIONAL REQUIREMENTS

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