Methylbenzethonium 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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C₂₈H₄₄CINO₂ . H₂O  480.12

C₂₈H₄₄CINO₂  462.12

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

Benzyldimethyl[2-[2-[[4-(1,1,3,3-tetramethylbutyl)tolyl] oxy]ethoxy]ethyl]ammonium chloride monohydrate CAS RN^®: 1320-44-1; UNII: WOA57K8S5V.

Anhydrous CAS RN^®: 25155-18-4; UNII: 4XKK0M5H9M.

1 DEFINITION

Methylbenzethonium Chloride contains NLT 97.0% and NMT 103.0% of C₂₈H₄₄CINO₂, calculated on the dried basis.

2 IDENTIFICATION

A. PROCEDURE

Analysis: To 1 mL of solution (1 in 100) 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 and soluble in 6 N ammonium hydroxide, is formed.

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

3 ASSAY

Change to read:

3.1 PROCEDURE

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

Mobile phase: Acetonitrile and Buffer (45:55)

Standard solution: 0.15 mg/mL of USP Methylbenzethonium Chloride RS in Mobile phase

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

Sample solution: 0.15 mg/mL of methylbenzethonium chloride in Mobile phase

Chromatographic system

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm x 15-cm; 5-µm packing L7

Column temperature: 40°

Flow rate: 1 mL/min

Injection size: 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 5.0 between the benzethonium and methylbenzethonium peaks

Tailing factor: NMT 1.8 for the methylbenzethonium peak

Relative standard deviation: NMT 0.5% for the methylbenzethonium peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methylbenzethonium chloride (C₂₈H₄₄CINO₂ (ERR 1-Nov-2023)) in the portion of Methylbenzethonium Chloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of methylbenzethonium from the Sample solution

r_S = peak response of methylbenzethonium from the Standard solution

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

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

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

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

5 SPECIFIC TESTS

MELTING RANGE OR TEMPERATURE (741): 159°-163°, the specimen having been previously dried

LOSS ON DRYING (731): Dry a sample at 105° for 4 h: it loses NMT 5.0% of its weight.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Benzethonium Chloride RS

USP Methylbenzethonium Chloride RS