Prazosin 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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C₁₉H₂₁N₅O₄ . HCl 419.86

Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)-, monohydrochloride;

1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl)piperazine monohydrochloride  CAS RN^®: 19237-84-4; UNII: X0Z7454B90.

1 DEFINITION

Prazosin Hydrochloride contains NLT 97.0% and NMT 103.0% of prazosin hydrochloride (C₁₉H₂₁N₅O₄ . HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

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

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

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

3 ASSAY

3.1 Procedure

[Caution—Care should be taken to prevent inhaling particles of Prazosin Hydrochloride and to prevent its contacting any part of the body.]

Mobile phase: Methanol, glacial acetic acid, and water (700:10:300). Add 0.2 mL of diethylamine to 1 L of Mobile phase such that the retention time of prazosin hydrochloride is 6–10 min.

Diluent: Methanol and water (70:30)

Standard stock solution: 1 mg/mL of USP Prazosin Hydrochloride RS in methanol

Standard solution: 30 µg/mL of USP Prazosin Hydrochloride RS in Diluent from the Standard stock solution

Sample stock solution: 1 mg/mL of Prazosin Hydrochloride in methanol

Sample solution: 30 µg/mL of Prazosin Hydrochloride in Diluent from Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 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 L3

Flow rate: Adjusted to obtain a retention time of 6–10 min for prazosin

Injection volume: 5 µL

Run time: NLT 2 times the retention time of the prazosin peak

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.10%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of prazosin hydrochloride (C₁₉H₂₁N₅O₄ . HCl) in the portion of Prazosin Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of prazosin from the Sample solution

r_S = peak response of prazosin from the Standard solution

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

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

Acceptance criteria: 97.0%–103.0% calculated on the anhydrous basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉

Sample: 1 g of Prazosin Hydrochloride

Acceptance criteria: NMT 0.4%

[Note—Save the residue for the test for Iron.]

4.2 Iron

Standard stock solution: Dissolve 100 mg of iron wire in 10 mL of hydrochloric acid with the aid of boiling. Cool, transfer to a 1000-mL volumetric flask, and dilute with water to volume.

Standard solution: 4.0 µg/mL of iron in 0.2 N nitric acid from Standard stock solution

Sample solution: Dissolve the residue obtained in the test for Residue on Ignition in 20 mL of 2 N nitric acid. Slowly evaporate this solution to approximately 5 mL; transfer to a 25-mL volumetric flask, using 0.2 N nitric acid as a wash solvent; and dilute with 0.2 N nitric acid to volume.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption

Analytical wavelength: 248 nm

Lamp: Iron hollow-cathode

Flame: Air–acetylene

Blank: Water

Analysis: Determine the absorbances of the Standard solution and the Sample solution against the Blank.

Acceptance criteria: The absorbance of the Sample solution is NMT that of the Standard solution (0.010%).

4.3 Nickel

Standard stock solution: Dissolve 100 mg of nickel in 10 mL of nitric acid with the aid of boiling. Cool, transfer to a 1000-mL volumetric flask, and dilute with water to volume.

Standard solution: 4.0 µg/mL of nickel in 0.2 N nitric acid from Standard stock solution

Sample solution: Prepare as directed in the test for Iron.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption

Analytical wavelength: 232 nm

Lamp: Nickel hollow-cathode

Flame: Air–acetylene

Blank: Water

Analysis: Determine the absorbances of the Standard solution and the Sample solution against the Blank.

Acceptance criteria: The absorbance of the Sample solution is NMT that of the Standard solution (0.010%).

Change to read:

4.4 Organic Impurities

Buffer: 3.48 g/L of sodium pentanesulfonate and 3.64 g/L of tetramethylammonium hydroxide. Adjust with glacial acetic acid to a pH of 5.0.

Mobile phase: Methanol and Buffer (500:500)

System suitability solution: 0.032 mg/mL of USP Metoclopramide Hydrochloride RS and 0.004 mg/mL of USP Prazosin Hydrochloride RS in Mobile phase

Standard solution: 1 µg/mL of USP Prazosin Hydrochloride RS in Mobile phase

Sensitivity solution: 0.5 (ERR 1-Jan-2022) µg/mL of USP Prazosin Hydrochloride RS in Mobile phase from the Standard solution

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 6 times the retention time of the prazosin peak

System suitability

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

[Note—The relative retention times of metoclopramide and prazosin are 0.55 and 1.00, respectively.]

Suitability requirements

Resolution: NLT 8 between the metoclopramide and prazosin peaks, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Prazosin Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of prazosin from the Standard solution

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

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

Acceptance criteria

Each individual impurity: NMT 0.2%

Total impurities: NMT 0.5%.

The reporting threshold is 0.05%.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I

Anhydrous form: NMT 2.0%

Polyhydrate form: 8.0%–15.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Labeling: Label it to indicate whether it is anhydrous or is the polyhydrate.

USP Reference Standards 〈11〉

USP Metoclopramide Hydrochloride RS

USP Prazosin Hydrochloride RS