Phenoxybenzamine Hydrochloride Capsules
• A. Ultraviolet Absorption
DEFINITION
Phenoxybenzamine Hydrochloride Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of phenoxybenzamine hydrochloride (C18H22ClNO·HCl).
IDENTIFICATION
Delete the following:
• The UV absorption spectrum of the solution exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Phenoxybenzamine Hydrochloride RS, concomitantly measured. The ratio A268/A272 of the maximum at 268 ± 2 nm and the minimum at 272 ± 2 nm is between 1.75 and 1.95.USP35
The UV absorption spectrum of the solution exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Phenoxybenzamine Hydrochloride RS, concomitantly measured. The ratio A268/A272 of the maximum at 268 ± 2 nm and the minimum at 272 ± 2 nm is between 1.75 and 1.95.USP35
Add the following:
• A. Ultraviolet Absorption
Analytical wavelengths:
268 and 272 nm
Sample solution:
0.15 mg/mL of phenoxybenzamine hydrochloride in acidic alcohol (1 in 1000 solution of hydrochloric acid in alcohol)
Acceptance criteria:
The ratio A268/A272 of the maximum at 268 ± 2 nm and the minimum at 272 ± 2 nm is between 1.75 and 1.95.USP35
USP35
ASSAY
• Procedure
Solution A:
2.2 mg/mL of anhydrous monobasic sodium phosphate in water. Adjust with concentrated phosphoric acid to a pH of 3.0.
Mobile phase:
Filtered and degassed mixture of Solution A and acetonitrile (45:55)
Standard solution:
0.2 mg/mL of USP Phenoxybenzamine Hydrochloride RS in acetonitrile. [Note—Sonicate if necessary. ]
System suitability solution:
10 mL of the Standard solution and 0.5 mL of 0.1 N sodium hydroxide taken in a vial. [Note—Basic solutions of phenoxybenzamine hydrochloride will produce the known degradant, tertiary amine phenoxybenzamine—the second major peak that elutes before the phenoxybenzamine peak and has a relative retention time of about 0.3 min—and an unknown related substance. Severe degradation of the drug substance will be observed if the solution is allowed to stand for more than 1 h. ]
Sample solution:
0.2 mg/mL of phenoxybenzamine hydrochloride in acetonitrile. Remove, as completely as possible, the contents of NLT 20 Capsules. 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.
Chromatographic system
Mode:
LC
Detector:
UV 268 nm
Column:
4.6-mm × 150-cm; packing L7
Column temperature:
Maintained at room temperature
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 4 between phenoxybenzamine hydrochloride and the unknown peak that elutes after the phenoxybenzamine peak (at about 9.4 min), System suitability solution
Relative standard deviation:
NMT 2% for an average of five injections determined from the phenoxybenzamine hydrochloride peak, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of phenoxybenzamine hydrochloride (C18H22ClNO·HCl) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Phenoxybenzamine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = concentration of phenoxybenzamine hydrochloride in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
0.1 N hydrochloric acid; 500 mL
Apparatus 1:
100 rpm
Time:
45 min
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.
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 (9:11)
Chromatographic system
Mode:
LC
Detector:
UV 268 nm
Column:
4.6-mm × 150-cm; packing L7
Column temperature:
Maintained at room temperature
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2%
Calculate the percentage of the labeled amount of phenoxybenzamine hydrochloride dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of 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 (C18H22ClNO·HCl) is dissolved.
• Uniformity of Dosage Units 905
905
Procedure for content uniformity
Solution A, Mobile phase, Standard solution, and Chromatographic system:
Proceed as directed in the Assay.
Sample solution:
0.2 mg/mL. Carefully open 10 Capsules, and transfer each immediately into separate volumetric flasks, including the Capsule shells. Add acetonitrile, to about 60% of the volume of the flask, and sonicate for 15 min with occasional stirring. Cool the flask, and dilute with acetonitrile to volume to achieve a concentration of 0.2 mg/mL. [Note—The Capsule shell does not dissolve. ]
Cool, dilute with acetonitrile to volume, mix, and pass through a nylon membrane filter of 0.45-µm pore size, discarding the first few mL of the filtrate.
Analysis
Samples:
Standard solution and Sample solution
Calculate the quantity of phenoxybenzamine hydrochloride in the Capsules taken:
Result = (rU/rS) × (CS/CU) × T
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Phenoxybenzamine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = concentration of phenoxybenzamine hydrochloride in the Sample solution, based on the labeled quantity per Capsule and the extent of dilution (mg/mL) |
| T | = | = labeled quantity of phenoxybenzamine hydrochloride in the Capsules taken (mg) |
Acceptance criteria:
Meets the requirements
IMPURITIES
Organic Impurities
• Procedure
Solution A, Mobile phase, Standard solution, System suitability solution, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each individual impurity:
Result = (rU/rT) × (1/F) × 100
| rU | = | = peak response for the individual impurity from the Sample solution |
| rT | = | = sum of all peak responses from the Sample solution |
| F | = | = relative response factor, which is 1.1 for the known degradant, phenoxybenzamine tertiary amine, and 1 for all other individual impurities |
Acceptance criteria
Individual impurities:
NMT 0.5% of phenoxybenzamine tertiary amine; NMT 0.1% of any other specified or unspecified individual impurity (degradant)
Total impurities:
NMT 0.5%, specified and unspecified
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers.
• USP Reference Standards 11
11
USP Phenoxybenzamine Hydrochloride RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4290
Pharmacopeial Forum: Volume No. 36(6) Page 1562