Brompheniramine Maleate

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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C₁₆H₁₉BrN₂ · C₄H₄O₄                  435.31

2-Pyridinepropanamine, γ-(4-bromophenyl)-N,N-dimethyl-, (±)-, (Z)-2-butenedioate (1:1);

(±)-2-p-Bromo-α-2-(dimethylamino)ethylbenzylpyridine maleate (1:1) CAS RN: 980-71-2; UNII: IXA7C9ZN03.

1 DEFINITION

Brompheniramine Maleate, dried at 105° for 3 h, contains NLT 98.0% and NMT 102.0% of brompheniramine maleate (C₁₆H₁₉BrN₂ · C₄H₄O₄)

2 IDENTIFICATION

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

B. The retention times of the maleic acid and brompheniramine peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: 5.44 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 3.0 ± 0.1.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Solution A (5:95)

System suitability stock solution: 0.02 mg/mL each of USP Pheniramine Maleate RS, USP Chlorpheniramine Maleate RS, and USP

Chlorpheniramine Related Compound B RS in Diluent. Sonicate for 1 min.

System suitability solution: 0.5 mg/mL of USP Brompheniramine Maleate RS and 2 µg/mL each of USP Pheniramine Maleate RS, USP

Chlorpheniramine Maleate RS, and USP Chlorpheniramine Related Compound B RS in Diluent, prepared as follows. Transfer 5.0 mg of USP Brompheniramine Maleate RS to a 10-mL volumetric flask, add 5.0 mL of Diluent, and 1.0 mL of the System suitability stock solution, and dilute with Diluent to volume.

Standard solution: 0.5 mg/mL of USP Brompheniramine Maleate RS in Diluent. Sonicate for 1 min.

Sample solution: 0.5 mg/mL of Brompheniramine Maleate in Diluent. Sonicate for 1 min.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

[Note—The relative retention times for maleic acid and brompheniramine are 0.18 and 1.0, respectively.]

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between chlorpheniramine and brompheniramine; and NLT 2.0 between chlorpheniramine related compound B and

pheniramine, System suitability solution

Tailing factor: NMT 2.0 for brompheniramine, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of brompheniramine maleate (C₁₆H₁₉BrN₂ · C₄H₄O₄) in the portion of Brompheniramine Maleate taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of brompheniramine from the Sample solution

r_s = peak response of brompheniramine from the Standard solution

C_s = concentration of USP Brompheniramine Maleate RS in the Standard solution (mg/mL)

C_u = concentration of Brompheniramine Maleate in the Sample solution (mg/mL)

Acceptance criteria: NLT 98.0%–NMT 102.0% on the previously dried basis

Acceptance criteria: NLT 98.0%-NMT 102.0% on the previously dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.2%

ORGANIC IMPURITIES

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

Standard solution: 2.7 µg/mL of USP Brompheniramine Maleate RS in Diluent, equivalent to 2.0 µg/ml of brompheniramine. Sonicate 1 min.

Sensitivity solution: 0.74 µg/mL of USP Pheniramine Maleate RS in Diluent

Sample solution: 0.5 mg/mL of Brompheniramine Maleate in Diluent. Sonicate for 1 min.

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 1.5 between chlorpheniramine and brompheniramine; and NLT 2.0 between chlorpheniramine related compound B and pheniramine, System suitability solution

Signal-to-noise ratio: NLT 10 for pheniramine, Sensitivity solution

Relative standard deviation: NMT 5.0% for brompheniramine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Brompheniramine Maleate taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of brompheniramine from the Standard solution

C_s = concentration of brompheniramine in the Standard solution (mg/mL)

C_u = concentration of Brompheniramine Maleate in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any peak having areas less than 0.05% of brompheniramine.

Table 2

^a Salt counter ion is included in the table for identication purposes only.

^b Di(pyridin-2-yl)amine. Used only to establish the system suitability.

5 SPECIFIC TESTS

Change to read:

OPTICAL ROTATION (781A), Angular Rotation _{(ERR 1-MAY-2024)}

Sample: 100 mg/mL in water at 20°

Acceptance criteria: -0.2° to +0.2°, measured in a 20-cm tube

PH (791)

Sample: 10 mg/mL

Acceptance criteria: 4.0-5.0

LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS (11)

USP Brompheniramine Maleate RS

USP Chlorpheniramine Maleate RS

USP Chlorpheniramine Related Compound B. RS

Di(pyridin-2-yl)amine.

C₁₀H₉N₃            171.20

USP Pheniramine Maleate RS