Levobunolol Hydrochloride

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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1(2H)-Naphthalenone, 5-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-3,4-dihydro-, hydrochloride, (–)-(S);

(−)-5-[3-(tert-Butylamino)-2-hydroxypropoxy]-3,4-dihydro-1(2H)-naphthalenone hydrochloride CAS RN®: 27912-14-7; UNII: O90S49LDHH.

1 DEFINITION

Levobunolol Hydrochloride contains NLT 98.0% and NMT 102.0% of levobunolol hydrochloride (C₁₇H₂₅NO₃· HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 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.

C. Identification Tests—General, Chloride〈191〉: Meets the requirements

3 ASSAY

Procedure

Solution A: 5 mM sodium 1-heptanesulfonate in methanol

Solution B: 5 mM sodium 1-heptanesulfonate in water

Mobile phase: Solution A, 0.5 M sulfuric acid, and Solution B (53:1:47)

Standard solution: 100 μg/mL of USP Levobunolol Hydrochloride RS in Mobile phase

Sample solution: 100 μg/mL of Levobunolol Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 223 nm

Column: 3.9 mm × 25 cm; 10-μm packing L7

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 levobunolol hydrochloride (C₁₇H₂₅NO₃ · HCl) in the portion of Levobunolol Hydrochloride 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 Levobunolol Hydrochloride RS in the Standard solution (μg/mL)

C_U = concentration of Levobunolol Hydrochloride in the Sample solution (μg/mL)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Solution A, Solution B, and Mobile phase: Proceed as directed in the Assay.

System suitability solution: 50 μg/mL each of USP Levobunolol Hydrochloride RS and USP Atenolol RS in Mobile phase

Standard solution: 5 μg/mL of USP Levobunolol Hydrochloride RS in Mobile phase

Sample solution: 1 mg/mL of Levobunolol Hydrochloride in Mobile phase

Chromatographic system: Proceed as directed in the Assay using Mobile phase.

Run time: 3 times the retention time of levobunolol

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 8 between levobunolol and atenolol peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Levobunolol Hydrochloride taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of levobunolol from the Standard solution

C_S = concentration of USP Levobunolol Hydrochloride RS in the Standard solution (μg/mL)

C_U = concentration of Levobunolol Hydrochloride in the Sample solution (μg/mL)

Acceptance criteria

Individual impurity: NMT 0.5%

Total impurities: NMT 1%

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 30 mg/mL in methanol

Acceptance criteria: −19° to −20°

pH 〈791〉

Sample: 50 mg/mL

Acceptance criteria: 4.5–6.5

Loss on Drying 〈731〉

Sample: 1 g

Analysis: Dry under vacuum over phosphorus pentoxide at 110° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Protect from light. Store at room temperature.

USP Reference Standards 〈11〉

USP Atenolol RS

USP Levobunolol Hydrochloride RS