10/17/24, 12:28 PM USP-NF Brimonidine Tartrate
Printed on: Thu Oct 17 2024, 12:27:57 pm
Printed by: OPHTH PHARMA
Status: Currently Official on 17-Oct-2024
Official Date: Official as of 01-May-2020
Document Type: USP Monographs
DocId: GUID-0E796674-ADAC-4ECF-9D58-498229A370E6_6_en-US
DOI: https://doi.org/10.31003/USPNF_M10200_06_01
DOI Ref: ab3t1
Printed from: https://online.uspnf.com/uspnf/document/1_GUID-0E796674-ADAC-4ECF-9D58-498229A370E6_6_en-US
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Brimonidine Tartrate
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.
DEFINITION
Brimonidine Tartrate contains NLT 98.0% and NMT 102.0% of brimonidine tartrate (C11H10BrN5 · C4H6O6), calculated on the dried basis.
IDENTIFICATION
Change to read:
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• A.▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A, 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.
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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
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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
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(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 264 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Column temperature: 30°
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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 = (rU/rS) × (CS/CU) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
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10/17/24, 12:28 PM USP-NF Brimonidine Tartrate
CS = concentration of USP Brimonidine Tartrate RS in the Standard solution (mg/mL)
CU = concentration of Brimonidine Tartrate in the Sample solution (mg/mL)
Acceptance criteria: 98.0%–102.0% on the dried basis
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
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Calculate the percentage of each impurity in the portion of Brimonidine Tartrate taken:
Result = (rU/rS) × (CS/CU) × 100
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rU = peak response of each individual impurity from the Sample solution
rS = peak response of brimonidine from the Standard solution
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CS = concentration of USP Brimonidine Tartrate RS in the Standard solution (mg/mL)
CU = 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%.
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Table 1
Relative Acceptance
Retention Criteria,
Name Time NMT (%)
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Desbromobrimonidinea 0.86 0.1
Brimonidine 1.00 —
Any individual
unspecified —
impurity 0.1
Total impurities — 0.3
a N-(Quinoxalin-6-yl)imidazolidin-2-imine.
SPECIFIC TESTS
• Optical Rotation 〈781S〉, Procedures, Specific Rotation
Sample solution: 10 mg/mL in water
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10/17/24, 12:28 PM USP-NF Brimonidine Tartrate
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%
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
Auxiliary Information - Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
BRIMONIDINE TARTRATE Documentary Standards Support SM32020 Small Molecules 3
Chromatographic Database Information: Chromatographic Database
Most Recently Appeared In:
Pharmacopeial Forum: Volume No. PF 42(4)
Current DocID: GUID-0E796674-ADAC-4ECF-9D58-498229A370E6_6_en-US
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DOI: https://doi.org/10.31003/USPNF_M10200_06_01
DOI ref: ab3t1
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