Brimonidine Tartrate

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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C₁₁H₁₀BrN₅  · C₄H₆O₆             442.22

6-Quinoxalinamine, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1);

5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline l-tartrate (1:1). CAS RN: 70359-46-5.

1 DEFINITION

Brimonidine Tartrate contains NLT 98.0% and NMT 102.0% of brimonidine tartrate (C₁₁H₁₀BrN₅  · C₄H₆O₆), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 1974, 197K, or 197M _{(CN 1-May-2020)}

B. 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

PROCEDURE

Protect the solutions containing brimonidine tartrate from light.

Mobile phase: In a 1-L volumetric flask, dissolve 2.6 g of sodium 1-heptanesulfonate in 310 mL of methanol, add 2.5 mL of triethylamine and

7.5 mL of glacial acetic acid, and dilute with water to volume.

Standard solution: 1.3 mg/mL of USP Brimonidine Tartrate RS in water

Sample solution: 1.3 mg/mL of Brimonidine Tartrate in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 264 nm

Column: 4.6-mm x 25-cm; 5-µm packing 11

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of brimonidine tartrate (C₁₁H₁₀BrN₅  · C₄H₆O₆) in the portion of Brimonidine Tartrate taken:

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

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Brimonidine Tartrate RS in the Standard solution (mg/mL)

C_u = concentration of Brimonidine Tartrate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.3%

ORGANIC IMPURITIES

Protect the solutions containing brimonidine tartrate and related substances from light.

Mobile phase: Proceed as directed in the Assay.

System suitability solution: 1.3 mg/mL of USP Brimonidine Tartrate RS and 1.3 µg/mL of USP Brimonidine Related Compound E RS in water

Sensitivity solution: 0.65 µg/mL of USP Brimonidine Tartrate RS in water

Standard solution: 1.3 µg/mL of USP Brimonidine Tartrate RS in water

Sample solution: 1.3 mg/mL of Brimonidine Tartrate in water

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 3 times the retention time of brimonidine

System suitability

Samples: System suitability solution and Sensitivity solution

[NOTE-The relative retention times for brimonidine related compound E and brimonidine are about 0.93 and 1.00, respectively.]

Suitability requirements

Resolution: NLT 1.5 between brimonidine related compound E and brimonidine, System suitability solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Brimonidine Tartrate taken:

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

r_u = peak response of each individual impurity from the Sample solution

r_s = peak response of brimonidine from the Standard solution

C_s = concentration of USP Brimonidine Tartrate RS in the Standard solution (mg/mL)

C_u = concentration of Brimonidine Tartrate in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. Disregard the tartrate peak at a relative retention time of 0.09. The reporting threshold is 0.05%.

Table 1

^a N-(Quinoxalin-6-yl)imidazolidin-2-imine.

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 10 mg/mL in water

Acceptance criteria: +9.0° to +10.5°

Loss on Drying 〈731〉

Analysis: Dry 1 g at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers, and store at room temperature.

USP Reference Standards 〈11〉

USP Brimonidine Tartrate RS

USP Brimonidine Related Compound E RS

2-(5-Bromoquinoxalin-6-yl)guanidine.

C₉H₈BrN₅         266.10