Propranolol Hydrochloride Injection

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

Propranolol Hydrochloride Injection is a sterile solution of Propranolol Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of propranolol hydrochloride (C₁₆H₂₁NO₂ · HCl).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Add the following:

▲B. The UV spectrum of the major peak of the Diluted sample solution corresponds to that of the Diluted standard solution, as obtained in the Assay.▲ (USP 1-Dec-2022)

3 ASSAY

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Procedure

▲Mobile phase: Dissolve 1.6 g of sodium dodecyl sulfate and 0.3 g of tetrabutylammonium phosphate in a mixture consisting 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: 0.1 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase. Sonicate to dissolve, if necessary.

Diluted standard solution: 0.02 mg/mL of USP Propranolol Hydrochloride RS in Mobile phase from Standard solution.

Sample solution: Nominally 0.1 mg/mL of propranolol hydrochloride in Mobile phase from a volume of the Injection.

Diluted sample solution: Nominally 0.02 mg/mL of propranolol hydrochloride in Mobile phase from Sample solution.▲

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 292 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Flow rate: 1.8 mL/min

Injection volume: 50 µL

Run time: NLT 9 times the retention time of propranolol

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution, Diluted standard solution, Sample solution, and Diluted sample solution

[Note—The Diluted standard solution and Diluted sample solution are used for Identification B.]

Calculate the percentage of the labeled amount of propranolol hydrochloride (C₁₆H₂₁NO₂ · HCl) in the portion of Injection 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 = nominal concentration of propranolol hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

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▲Organic Impurities

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

System suitability solution:

1 µg/mL of USP Propranolol Related Compound A RS and

500 µg/mL of USP Propranolol Hydrochloride RS

in Mobile phase

Standard solution:

1 µg/mL of USP Propranolol Hydrochloride RS in Mobile phase

Sensitivity solution:

0.5 µg/mL of USP Propranolol Hydrochloride RS in Mobile phase from Standard solution

Sample solution:

Nominally 500 µg/mL of propranolol hydrochloride in Mobile phase from a volume of the Injection

System suitability

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

[Note—The relative retention times for propranolol related compound A and propranolol are 0.6 and 1.0, respectively.]

Suitability requirements

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

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any unspecified degradation product in the portion of Injection taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of any unspecified degradation product from the Sample solution

rₛ = peak response of propranolol from the Standard solution

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

Cᵤ = nominal concentration of propranolol hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 1. The reporting threshold is 0.1%.

▲ (USP 1-Dec-2022)

5 SPECIFIC TESTS

Change to read:

Bacterial Endotoxins Test 〈85〉: ▲Meets the requirements▲ (USP 1-Dec-2022)

Add the following:

▲Particulate Matter in Injections 〈788〉: Meets the requirements▲ (USP 1-Dec-2022)

pH 〈791〉: 2.8–4.0

Add the following:

▲Sterility Tests 〈71〉: Meets the requirements▲ (USP 1-Dec-2022)

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in single-dose, light-resistant containers, preferably of Type I glass. ▲Store at controlled room temperature. Protect from freezing or excessive heat.▲ (USP 1-Dec-2022)

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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-Dec-2022)