Brinzolamide

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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C₁₂H₂₁N₃O₅S₃          383.51

2H-Thieno[3,2-e]-1,2-thiazine-6-sulfonamide, 4-(ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-, 1,1-dioxide, (R)-;

(R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide CAS RN: 138890-62-7; UNII: 9451Z89515.

1 DEFINITION

Brinzolamide contains NLT 98.0% and NMT 102.0% of brinzolamide (C₂H₂,NOS), calculated on the dried basis.

2 IDENTIFICATION

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

B. The retention time of the major peak of the Sample solution corresponds to that of the System suitability solution, as obtained in Limit of Brinzolamide Related Compound A.

3 ASSAY

PROCEDURE

Buffer: Add 4.0 mL of triethylamine to 1000 mL of water, and acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (25:75)

Standard solution: 0.1 mg/mL of USP Brinzolamide RS in Mobile phase

Sample solution: 0.1 mg/ml. of Brinzolamide in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1200 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of brinzolamide (C₁₂H₂₁N₃O₅S₃) in the portion of Brinzolamide 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 Brinzolamide RS in the Standard solution (mg/mL)

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

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

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

4.1 LIMIT OF BRINZOLAMIDE RELATED COMPOUND A

Mobile phase: Dehydrated alcohol, chromatographic hexane, methanol, and diethylamine (55:40:5:0.2)

System suitability solution: 0.4 mg/mL of USP Brinzolamide RS and 0.02 mg/mL of USP Brinzolamide Related Compound A RS in dehydrated alcohol

Sample solution: 0.5 mg/mL of Brinzolamide in dehydrated alcohol

Chromatographic system

(See Chromatography (621). System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; packing L51

Flow rate: 0.75 mL/min

Injection volume: 5 µL

System suitability

Sample: System suitability solution

[NOTE-The relative retention times for brinzolamide and brinzolamide related compound A are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.8 between brinzolamide and brinzolamide related compound A peaks

Column efficiency: NLT 2000 theoretical plates for the brinzolamide peak

Tailing factor: NMT 1.8 for the brinzolamide peak

Analysis

Sample: Sample solution

Calculate the percentage of brinzolamide related compound A in the portion of Brinzolamide taken:

Result = (r_u /r_t ) × 100

r_u = peak response for brinzolamide related compound A

r_t = sum of the peak responses for brinzolamide and brinzolamide related compound A

Acceptance criteria: NMT 0.5%

4.2 ORGANIC IMPURITIES

Buffer: Prepare as directed in the Assay.

Mobile phase A: Prepare as directed for Mobile phase in the Assay.

Mobile phase B: Acetonitrile and Buffer (35:65)

System suitability solution: 0.1 mg/mL each of USP Brinzolamide RS and USP Brinzolamide Related Compound B RS in Mobile phase A

Sample solution: 1 mg/mL of Brinzolamide in Mobile phase A

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

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

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Sample: Systern suitability solution

Use Mobile phase A.

[NOTE-The relative retention times for brinzolamide related compound B and brinzolamide are 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between the brinzolamide and brinzolamide related compound B peaks

Column efficiency: NLT 1200 theoretical plates for the brinzolamide peak

Tailing factor: NMT 2.0 for the brinzolamide peak

Analysis 1

Use Mobile phase A.

Sample: Sample solution

Allow the elution to continue for 20 min, and measure the areas for all the peaks, excluding the peaks of Mobile phase A.

Calculate the percentage of each impurity in the portion of Brinzolamide taken:

Result = (r_u /r_t ) × 100

r_u = peak response for each impurity

r_t = sum of all the peak responses

Acceptance criteria 1: NMT 0.3% for any individual impurity

Analysis 2

Use Mobile phase B.

Sample: Sample solution

Allow the elution to continue for 20 min, and measure the areas for brinzolamide and all the peaks having a relative retention greater than 6.

Calculate the percentage of each impurity in the portion of Brinzolamide taken:

Result = (r_u /r_t ) × 100

r_u = peak response for each impurity

r_t = sum of all the peak responses

Acceptance criteria 2: NMT 0.3% for any individual impurity; NMT 1.0% for total impurities from Analysis 1 and Analysis 2

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry under vacuum at 100-105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

Change to read:

USP REFERENCE STANDARDS (11)

USP Brinzolamide RS

USP Brinzolamide Related Compound A RS

(S)-4-(Ethylamino)-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide. _{(CN 1-Dec-2023)}

C₁₂H₂₁N₃O₅S₃                     383.50 _{(CN 1-Dec-2023)}

USP Brinzolamide Related Compound B RS

(R)-4-Amino-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide oxalate.

C₁₀H₁₇N₃O₅S₃ C₂H₂O₄       445.48 (CN 1-Dec-2023)