Propranolol 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 DEFINITION

Change to read:

Propranolol Hydrochloride contains NLT 98.0% and NMT ▲102.0%▲ (USP 1-May-2020) of propranolol hydrochloride (C₁₆H₂₁NO₂ · 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 〈191〉, Chemical Identification Tests, Chloride: Meets the requirements

3 ASSAY

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Procedure

▲Mobile phase: Mix 1.6 g of sodium dodecyl sulfate and 0.31 g of tetrabutylammonium phosphate in a mixture of 1 mL of sulfuric acid, 450 mL of water, and 550 mL of acetonitrile. Adjust with 2 N sodium hydroxide solution to a pH of 3.3.

Standard solution: 0.2 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase. Sonication may be needed to aid dissolution.

Sample solution: 0.2 mg/mL of Propranolol Hydrochloride in Mobile phase. Sonication may be needed to aid dissolution.▲

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 292 nm

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

Flow rate: 1.8 mL/min

Injection volume: 20 µL

Run time: NLT 7 times the retention time of propranolol

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of propranolol hydrochloride (C₁₆H₂₁NO₂ · HCl) in the portion of Propranolol Hydrochloride taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of propranolol from the Sample solution

rₛ = peak response of propranolol from the Standard solution

Cₛ = concentration of USP Propranolol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Propranolol Hydrochloride in the Sample solution (mg/mL)

▲ (USP 1-May-2020)

Acceptance criteria: 98.0%–▲102.0%▲ (USP 1-May-2020) on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

▲Organic Impurities

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

System suitability solution:

0.002 mg/mL of USP Propranolol Related Compound A RS and

2 mg/mL of USP Propranolol Hydrochloride RS

in Mobile phase

Standard solution:

0.002 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase

Sensitivity solution:

0.001 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase from Standard solution

Sample solution:

2 mg/mL of Propranolol Hydrochloride in Mobile phase. Sonication may be needed to aid dissolution.

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note—The relative retention times for the impurities are listed in Table 1.]

Suitability requirements

Resolution: NLT 3.0 between propranolol and propranolol related compound A, System suitability solution

Relative standard deviation: NMT ▲5.0%,▲ (ERR 1-May-2020) Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified and unspecified impurity in the portion of Propranolol Hydrochloride taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

rᵤ = peak response of each specified and unspecified impurity from the Sample solution

rₛ = peak response of propranolol from the Standard solution

Cₛ = concentration of USP Propranolol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Propranolol Hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

a 3,3′-(Isopropylazanediyl)bis[1-(naphthalen-1-yloxy)propan-2-ol].

b 1,3-Bis(naphthalen-1-yloxy)propan-2-ol.

▲ (USP 1-May-2020)

5 SPECIFIC TESTS

Delete the following:

▲Melting Range or Temperature, Class Ia 〈741〉: 162°–165°▲ (USP 1-May-2020)

Delete the following:

▲Optical Rotation 〈781S〉, Specific Rotation

Sample solution: 40 mg/mL in water

Acceptance criteria: −1.0° to +1.0°▲ (USP 1-May-2020)

Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Propranolol Hydrochloride RS

▲USP Propranolol Related Compound A RS

3-(Naphthalen-1-yloxy)propane-1,2-diol.

C₁₃H₁₄O₃ 218.25▲ (USP 1-May-2020)