Acebutolol 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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C₁₈H₂₈N₂O₄·HCI 372.89

Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]-, monohydrochloride, (±)-;

(±)-3'-Acetyl-4'-[2-hydroxy-3-(isopropylamino)propoxy]-butyranilide monohydrochloride CAS RN®: 34381-68-5; UNII: B025Y34C54.

1 DEFINITION

Acebutolol Hydrochloride contains NLT 98.0% and NMT 102.0% of acebutolol hydrochloride (C₁₈H₂₈N₂O₄·HCI), 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 Standard solution, as obtained in the Assay.

Change to read:

C. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Chloride: Meets the requirements of the test for amine hydrochlorides

3 ASSAY

Change to read:

3.1 PROCEDURE

Mobile phase: Methanol, glacial acetic acid, and a 0.3% aqueous solution of sodium dodecyl sulfate (675:20:325)

Standard solution: 0.14 mg/mL of USP Acebutolol Hydrochloride RS in water

Sample solution: 0.14 mg/mL of Acebutolol Hydrochloride in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 30-cm; 10-µm (USP 1-May-2021) packing 11

Flow rate: 2 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

(USP 1-May-2021)

Tailing factor: NMT 2.5

Relative standard deviation: NMT (USP 1-May-2021) 0.73%

3.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of acebutolol hydrochloride (C₁₈H₂₈N₂O₄·HCI) in the portion of Acebutolol Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of acebutolol from the Sample solution

r_S = peak response of acebutolol from the Standard solution

C_S = concentration of USP Acebutolol Hydrochloride RS in the Standard solution (mg/mL)

CU = concentration of Acebutolol Hydrochloride in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Residue on Ignition 〈281〉

NMT 0.1%

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4.2 Organic Impurities

Solution A: Mix 2.0 mL of phosphoric acid and 3.0 mL of triethylamine, and dilute with water to 1 L.

Solution B: Acetonitrile and Solution A (50:50)

Mobile phase: See Table 1.

Standard stock solution 1: 0.2 mg/mL of USP Acebutolol Related Compound A RS prepared as follows. Dissolve a suitable amount of USP Acebutolol Related Compound A RS in a suitable volumetric flask, in 50% of the total volume of acetonitrile, and dilute with Solution A to volume.

Standard stock solution 2: 0.2 mg/mL of USP Acebutolol Related Compound B RS prepared as follows. Dissolve a suitable amount of USP Acebutolol Related Compound B RS in a suitable volumetric flask, in 50% of the total volume of acetonitrile, and dilute with Solution A to volume.

Standard solution A: 0.002 mg/mL of USP Acebutolol Hydrochloride RS in Solution A

Standard solution B: 0.004 mg/mL of USP Acebutolol Related Compound I RS in Solution A

Standard solution C: 0.002 mg/mL of USP Acebutolol Related Compound A RS in Solution A from Standard stock solution 1

Standard solution D: 0.004 mg/mL of USP Acebutolol Related Compound B RS in Solution A from Standard stock solution 2

System suitability solution: 0.4 µg/mL each of USP Acebutolol Hydrochloride RS and USP Acebutolol Related Compound I RS in Solution A from Standard solution A and Standard solution B

Sample solution: 2 mg/mL of Acebutolol Hydrochloride in Solution A

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.0-mm x 12.5-cm ; 5-µm packing L1

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection volume: 25 µL

System suitability

Samples: Standard solution A and System suitability solution

Suitability requirements

Resolution: NLT 7.0 between acebutolol and acebutolol related compound I, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution A

Analysis

Samples: Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Sample solution

Calculate the percentage of acebutolol related compound A, acebutolol related compound B, and acebutolol related compound I in the portion of Acebutolol Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of acebutolol related compound A, acebutolol related compound B, or acebutolol related compound I from the Sample solution

r_S = peak response of acebutolol related compound A, acebutolol related compound B, or acebutolol related compound I from Standard solution B, Standard solution C, or Standard solution D

C_S = concentration of USP Acebutolol Related Compound A RS, USP Acebutolol Related Compound B RS, or USP Acebutolol Related Compound I RS in Standard solution B, Standard solution C, or Standard solution D (mg/mL)

C_U = concentration of Acebutolol Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any unspecied impurity in the portion of Acebutolol Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecied impurity from the Sample solution

r_S = peak response of acebutolol from Standard solution A

C_S = concentration of USP Acebutolol Hydrochloride RS in Standard solution A (mg/mL)

C_U = concentration of Acebutolol Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

^a Total impurities include specied and unspecied impurities.

5 SPECIFIC TESTS

5.1 PH (791)

Sample solution: 10 mg/mL of Acebutolol Hydrochloride in water

Acceptance criteria: 4.5-7.0

5.2 LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Acebutolol Hydrochloride RS

USP Acebutolol Related Compound A RS

N-(3-Acetyl-4-hydroxyphenyl)butyramide.

C₁₂H₁₅NO₃ 221.25

USP Acebutolol Related Compound B RS

N-(3-Acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl acetamide.

C₁₆H₂₄N₂O₄ 308.37

USP Acebutolol Related Compound I RS

N-(3-Acetyl-4-[3-(ethylamino)-2-hydroxypropoxy]phenyl)butyramide.

C₁₇H₂₆N₂O₄ 322.40