Alfuzosin 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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C₁₉H₂₇N₅O₄· HCl 425.91

2-Furancarboxamide, N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-, monohydrochloride (±); (±)-N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furamide monohydrochloride    CAS RN®: 81403-68-1; UNII:  75046A1XTN.

1 DEFINITION

Alfuzosin Hydrochloride contains NLT 98.0% and NMT 102.0% of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

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

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

3 ASSAY

3.1 Procedure

[Note—Use low-actinic glassware.]

Solution A: 2 M sodium hydroxide

Solution B: 5.0 mL of perchloric acid in 900 mL of water. Adjust with Solution A to a pH of 3.5, and dilute with water to 1000 mL. Mobile phase: Acetonitrile and Solution B (30:70)

Diluent: Methanol and Solution A (500:3)

Standard stock solution: 0.5 mg/mL of USP Alfuzosin Hydrochloride RS in Diluent

Standard solution: 0.04 mg/mL of USP Alfuzosin Hydrochloride RS in Mobile phase from the Standard stock solution; the solution is stable for 14 h at 5°.

Sample stock solution: 0.5 mg/mL of Alfuzosin Hydrochloride in Diluent

Sample solution: 0.04 mg/mL of Alfuzosin Hydrochloride in Mobile phase from the Sample stock solution; the solution is stable for 14 h at 5°. Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Column temperature: 30°

Autosampler temperature: 5°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.0%

Tailing factor: NMT 1.5

3.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of alfuzosin hydrochloride (C₁₉H₂₇N₅O₄ · HCl) in the portion of Alfuzosin 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 Alfuzosin Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

4.1 Organic Impurities

Buffer: Dilute 5 mL of perchloric acid in 900 mL of water. Adjust with 2 M sodium hydroxide to a pH of 3.5, and dilute with water to 1 L. Mobile phase: Acetonitrile, tetrahydrofuran, and Buffer (20:1:80)

System suitability solution: 0.4 mg/mL of USP Alfuzosin System Suitability Mixture RS in Mobile phase

Sample solution: 0.40 mg/mL of Alfuzosin Hydrochloride in Mobile phase

Reference solution: 0.40 µg/mL of Alfuzosin Hydrochloride in Mobile phase from the Sample solution

4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Flow rate: 1.5 mL/min Injection volume: 10 µL System suitability

Sample: System suitability solution

Suitability requirements

Peak-to-valley ratio: The ratio of the height of the furamide analog peak to the height of the valley between the furamide analog peak and alfuzosin is NLT 5.

4.3 Analysis

Samples: Sample solution and Reference solution

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

Result = (r_U /r_S ) × (1/D) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of alfuzosin from the Reference solution

D = dilution factor between the Sample solution and the Reference solution, 1000

Acceptance criteria: See Table 1. [Note—Disregard any peak with an area less than 0.05%.]

Table 1

a N2-(3-Aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-2,4-diamine. 

b N-{3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}furan-2-carboxamide. 

c Furamide analog, a component of USP Alfuzosin System Suitability Mixture RS, is not a specied impurity.

5 SPECIFIC TESTS

Optical Rotation 〈781〉

Sample solution: 20 mg/mL in carbon dioxide-free water

Acceptance criteria: −0.10° to +0.10°

Water Determination, Method I 〈921〉: NMT 2.0%

pH 〈791〉

Sample solution: 20 mg/mL in carbon dioxide-free water

Acceptance criteria: 4.0–5.5

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Protect from light and humidity, and store at room temperature. • USP Reference Standards 〈11〉

USP Alfuzosin Hydrochloride RS

USP Alfuzosin System Suitability Mixture RS

Alfuzosin Hydrochloride containing approximately 0.4% furamide analog (N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl) (methyl)amino]propyl}furan-2-carboxamide), and about 0.4% deacylated alfuzosin (N2-(3-aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-2,4- diamine).