Benzethonium Chloride

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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C₂₇H₄₂ClNO₂  448.08

Benzenemethanaminium, N,N-dimethyl-N-[2-[2-[4-(1,1,3,3- tetramethylbutyl)phenoxy]ethoxy]ethyl]-, chloride;

Benzyldimethyl[2-[2-[p-(1,1,3,3-tetramethylbutyl)phenoxy] ethoxy]ethyl]ammonium chloride CAS RN^®: 121-54-0.

1 DEFINITION

Benzethonium Chloride contains NLT 97.0% and NMT 103.0% of benzethonium chloride (C27H42CINO₂), calculated on the dried basis.

2 IDENTIFICATION

A.

Sample solution: 10 mg/mL

Analysis: Add 2 mL of alcohol, 0.5 mL of 2 N nitric acid, and 1 mL of silver nitrate TS to 1 mL of the Sample solution.

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

Change to read:

B. ASPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K (CN 1-May-2020)

C. 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

3.1 PROCEDURE

Buffer: Dilute 20 mL of triethylamine with water to 1000 mL, and adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (42:58)

Diluent: Acetonitrile and water (42:58)

System suitability solution: 0.15 mg/mL each of USP Benzethonium Chloride RS and USP Methylbenzethonium Chloride RS in Diluent

Standard solution: 0.15 mg/mL of USP Benzethonium Chloride RS in Diluent

Sample solution: 0.15 mg/mL of Benzethonium Chloride in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 15-cm; 5-µm packing LZ

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: 1.5 times the retention time of the methylbenzethonium peak

System suitability

Sample: System suitability solution

[NOTE-The relative retention times for benzethonium and methylbenzethonium are 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 7.0 between the benzethonium and methylbenzethonium peaks

Tailing factor: NMT 2.0 for the benzethonium peak

Relative standard deviation: NMT 1.0% for the benzethonium peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of benzethonium chloride (C₂₇H₄₂ClNO₂) in the portion of Benzethonium Chloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of benzethonium from the Sample solution

r_S = peak response of benzethonium from the Standard solution 

C_S = concentration of USP Benzethonium Chloride RS in the Standard solution (mg/mL)

C_U = concentration of Benzethonium Chloride in the Sample solution (mg/mL)

Acceptance criteria: 97.0%-103.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

Change to read:

4.2 ORGANIC IMPURITIES

Buffer, Mobile phase, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 1 µg/mL of USP Benzethonium Chloride RS in Diluent

Sample solution: 1 mg/mL of Benzethonium Chloride in Diluent

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements: Proceed as directed in the Assay, except for Relative standard deviation.

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Benzethonium Chloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any individual impurity from the Sample solution

r_S = peak response of benzethonium from the Standard solution

C_S = concentration of USP Benzethonium Chloride RS in the Standard solution (mg/mL)

C_U = concentration of Benzethonium Chloride in the Sample solution (mg/mL)

Acceptance criteria

Total impurities: NMT (ERR 1-Feb-2019) 1.0%

5 SPECIFIC TESTS

5.1 LOSS ON DRYING (731)

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 5.0%

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS (11)

USP Benzethonium Chloride RS

USP Methylbenzethonium Chloride RS