Phenoxybenzamine Hydrochloride Capsules

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

Phenoxybenzamine Hydrochloride Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of phenoxybenzamine hydrochloride (C₁₈H₂₂CINO·HCI).

2 IDENTIFICATION

A. The UV absorption spectra of the phenoxybenzamine peak of the Sample solution exhibit maxima and minima at the same wavelengths as those of the corresponding peak from the Standard solution, as obtained in the Assay.

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

3 ASSAY

Change to read:

3.1 PROCEDURE

Solution A: 2.2 mg/mL of anhydrous monobasic sodium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: (USP 1-May-2022) Solution A and acetonitrile (45:55)

System suitability solution: 0.2 mg/mL of USP Phenoxybenzamine Hydrochloride RS, 1 µg/mL of USP Phenoxybenzamine Alcohol RS, and 50 µg/mL of USP Phenoxybenzamine Nitrile RS in acetonitrile. [NOTE-USP Phenoxybenzamine Alcohol RS is used for retention time verification.] (USP 1-May-2022)

Standard solution: 0.2 mg/mL of USP Phenoxybenzamine Hydrochloride RS in acetonitrile. [NOTE-Sonicate, if necessary.]

Sample solution: Nominally 0.2 mg/mL of phenoxybenzamine hydrochloride in acetonitrile prepared as follows. Remove, as completely as possible, the contents of Capsules (NLT 20). Transfer a portion of the mixed powder, equivalent to about 10 mg of phenoxybenzamine hydrochloride, to a 50-mL volumetric flask. Add about 40 mL of acetonitrile, and sonicate for 15 min with occasional swirling. Cool, and dilute with acetonitrile to volume to obtain the concentration, based on the label claim. Allow the sample to stand undisturbed for 30 min such that the undissolved material settles to the bottom. Transfer the top clear solution into HPLC vials, and use as the Sample solution.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 268 nm. For Identification A, use a diode array detector in the range of 240-340 nm.

Column: 4.6-mm x 15 (USP 1-May-2022) -cm; 5-µm packing 17

Flow rate: 1 mL/min

Injection volume: 10 µL

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for phenoxybenzamine alcohol, phenoxybenzamine, and phenoxybenzamine nitrile are about 0.2, 1.0, and 1.4, respectively.] (USP 1-MAY-2022)

Suitability requirements

Resolution: NLT 4 between phenoxybenzamine and phenoxybenzamine nitrile, (USP 1-May-2022) System suitability solution

Relative standard deviation: NMT 2%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of phenoxybenzamine hydrochloride (C₁₈H₂₂CINO·HCI) in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of phenoxybenzamine from the Sample solution

r_S = peak response of phenoxybenzamine from the Standard solution

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

C_U = nominal concentration of phenoxybenzamine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 1: 100 rpm

Time: 45 min

Buffer: 2.2 g/L of monobasic sodium phosphate in water. Adjust with phosphoric acid to a pH of 3.00 ± 0.05.

Mobile phase: Buffer and acetonitrile (45:55)

Standard solution: 0.02 mg/mL of USP Phenoxybenzamine Hydrochloride RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 268 nm

Column: 4.6-mm x 15 (USP 1-May-2022) -cm; packing L7

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2%

Analysis

Samples: Standard solution and Sample solution (USP 1 -May-2022)

Calculate the percentage of the labeled amount of phenoxybenzamine hydrochloride (C₁₈H₂₂CINO·HCI) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response of phenoxybenzamine from the Sample solution

r_S = peak response of phenoxybenzamine from the Standard solution

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

L = label claim (mg/Capsule)

V = volume of Medium, 500 mL

Tolerances: NLT 75% (Q) of the labeled amount of phenoxybenzamine hydrochloride (C₁₈H₂₂CINO·HCI) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A, Mobile phase, System suitability solution, Standard solution, (USP 1-May-2022) and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.4 µg/mL of USP Phenoxybenzamine Hydrochloride RS from Standard solution in acetonitrile

Sample solution: Nominally 0.4 mg/mL of phenoxybenzamine hydrochloride in acetonitrile prepared as follows. Transfer a portion of the mixed powder that is used for the Sample solution preparation in the Assay, equivalent to about 20 mg of phenoxybenzamine hydrochloride,

to a 50-mL volumetric flask. Add about 40 mL of acetonitrile, and sonicate to dissolve. Dilute with acetonitrile to volume. Allow the sample to stand undisturbed for 30 min such that the undissolved material settles to the bottom. Transfer the top clear solution into HPLC vials, and use as the Sample solution. (USP 1-May-2022)

System suitability

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

[NOTE-The relative retention times for phenoxybenzamine alcohol, phenoxybenzamine, and phenoxybenzamine nitrile are about 0.2, 1.0, and 1.4, respectively.] (USP 1-MAY-2022)

Suitability requirements

Resolution: NLT 4 between phenoxybenzamine and phenoxybenzamine nitrile, (USP 1-May-2022) System suitability solution

Relative standard deviation: NMT 2%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-May-2022)

Analysis

Sample: Sample solution

Calculate the percentage of phenoxybenzamine alcohol or any unspecified degradation product (USP 1-May-2022) in the portion of Capsules taken:

Result = (r_U/r_T) x (1/F) x 100

r_U = peak response of phenoxybenzamine alcohol or any unspecified degradation product (USP 1-May-2022) from the Sample solution

r_T = sum of all the peak responses from the Sample solution

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

6 ADDITIONAL REQUIREMENTS

Change to read:

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers. Store at controlled room temperature. (USP 1-May-2022)

Change to read:

6.2 USP REFERENCE STANDARDS (11)

USP Phenoxybenzamine Alcohol RS

2-[Benzyl(1-phenoxypropan-2-yl)amino]ethan-1-ol.

C₁₈H₂₃NO₂ 285.39 (USP 1-May-2022)

USP Phenoxybenzamine Hydrochloride RS

USP Phenoxybenzamine Nitrile RS

3-[Benzyl (1-phenoxypropan-2-yl)amino]propanenitrile.

C₁₉H₂₂N₂O 294.40 (USP 1-May-2022)