Phenoxybenzamine 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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C₁₈H₂₂CINO·HCI 340.29

Benzenemethanamine, N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl)-, hydrochloride;

N-(2-Chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine hydrochloride CAS RN^®: 63-92-3; UNII: X1IEG24OHL.

1 DEFINITION

Phenoxybenzamine Hydrochloride contains NLT 98.0% and NMT 102.0% of phenoxybenzamine hydrochloride (C₁₈H₂₂CINO·HCI), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

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: Dissolve 2.2 g of sodium phosphate, monobasic, anhydrous (ERR-1-Oct-2024) in 1 L of water. Adjust with phosphoric acid to a pH of 3.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.2 mg/mL of USP Phenoxybenzamine Hydrochloride RS and 50 µg/mL of USP Phenoxybenzamine Nitrile RS in Solution B

Standard solution: 0.2 mg/mL of USP Phenoxybenzamine Hydrochloride RS in Solution B

Sample solution: 0.2 mg/mL of Phenoxybenzamine Hydrochloride in Solution B

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 268 nm

Column: 4.6-mm x 15-cm; 3.5-µm packing L7

Autosampler temperature: 4°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times of phenoxybenzamine and phenoxybenzamine nitrile.]

Suitability requirements

Resolution: NLT 2.0 between phenoxybenzamine and phenoxybenzamine nitrile, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phenoxybenzamine hydrochloride (C₁₈H₂₂CINO·HCI) in the portion of Phenoxybenzamine Hydrochloride 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 = concentration of Phenoxybenzamine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

ORGANIC IMPURITIES

Solution A, Solution B, and Mobile phase: Prepare as directed in the Assay.

System suitability solution: 1.0 mg/mL of USP Phenoxybenzamine Hydrochloride RS and 10 µg/mL of USP Phenoxybenzamine Nitrile RS in Solution B

Standard solution: 1.0 µg/mL each of USP Phenoxybenzamine Hydrochloride RS and USP Phenoxybenzamine Alcohol RS in Solution B

Sensitivity solution: 0.5 µg/mL each of USP Phenoxybenzamine Hydrochloride RS and USP Phenoxybenzamine Alcohol RS from Standard solution in Solution B

Sample solution: 1000 µg/mL of Phenoxybenzamine Hydrochloride in Solution B

Chromatographic system: Proceed as directed in the Assay, except for the Detector.

Detector: UV 210 nm

System suitability

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

[NOTE-The relative retention times in Table 2 are provided as information that could aid in peak assignment.]

Table 2

^a 1-Benzyl-1-(1-phenoxypropan-2-yl)aziridin-1-ium. It can be formed in-situ under the chromatographic conditions.

Suitability requirements

Resolution: NLT 2.0 between phenoxybenzamine and phenoxybenzamine nitrile, System suitability solution

Relative standard deviation: NMT 5.0% for phenoxybenzamine alcohol and phenoxybenzamine, Standard solution

Signal-to-noise ratio: NLT 10 for phenoxybenzamine alcohol and phenoxybenzamine, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phenoxybenzamine alcohol in the portion of Phenoxybenzamine Hydrochloride taken:

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

r_U = peak response of phenoxybenzamine alcohol from the Sample solution

r_S = peak response of phenoxybenzamine alcohol from the Standard solution

C_S = concentration of USP Phenoxybenzamine Alcohol RS in the Standard solution (µg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Phenoxybenzamine Hydrochloride taken:

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

r_U = peak response of any unspecified impurity 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 (µg/mL)

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

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

Table 3

^a Exclude phenoxybenzamine aziridinium, if present.

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry under vacuum at 60° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers.

6.2 USP REFERENCE STANDARDS (11)

USP Phenoxybenzamine Alcohol RS

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

C₁₈H₂₃NO₂ 285.39

USP Phenoxybenzamine Hydrochloride RS

USP Phenoxybenzamine Nitrile RS

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

C₁₉H₂₂N₂O 294.40