Phentolamine Mesylate Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Phentolamine Mesylate Injection is a clear, colorless, sterile solution. It contains NLT 90.0% and NMT 105.0% of the labeled amount of phentolamine mesylate (C₁₇H₁₉N₃O·CH₄O₃S). It contains no preservatives.

2 IDENTIFICATION

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

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

3 ASSAY

3.1 PROCEDURE

Buffer: Transfer 10.2 g of monobasic potassium phosphate to a suitable container. Add 3000 mL of water to dissolve. Adjust with phosphoric acid to a pH of 2.5.

Solution A: Methanol and Buffer (20:80)

Solution B: Methanol and Buffer (70:30)

Mobile phase: See Table 1.

Table 1

Diluent: Transfer 1.36 g of sodium acetate and 0.5 g of ethylenediamine tetraacetate disodium dihydrate to a 1000-mL volumetric flask. Add 1000 mL of water to dissolve. Adjust with glacial acetic acid to a pH of 3.8.

Standard solution A: 0.22 mg/mL of USP Phentolamine Mesylate RS in Diluent. [NOTE-Sonication may be needed to aid the dissolution.]

Standard solution B: 0.22 mg/mL of USP Phentolamine Related Compound A RS in Diluent.

[NOTE-Sonication may be needed to aid the dissolution.]

Standard solution C: 0.22 mg/mL of USP Phentolamine Keto Analog RS prepared as follows. Transfer a suitable amount of USP Phentolamine Keto Analog RS in a suitable volumetric flask. Add methanol to 15% of the flask volume, and sonicate. Dilute with Diluent to volume.

System suitability solution: 0.22 mg/mL of USP Phentolamine Mesylate RS and 1.1 µg/mL each of USP Phentolamine Related Compound A RS from Standard solution B and USP Phentolamine Keto Analog RS from Standard solution C in Diluent

Sample solution: Nominally 0.24 mg/mL of phentolamine mesylate prepared from a suitable volume of the pooled Injection (NLT 4 cartridges)

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 232 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 4-µm packing L87

Flow rate: 1 mL/min

Injection volume: 10 µL

3.3 System suitability

Samples: Standard solution A and System suitability solution

[NOTE-The relative retention times for phentolamine keto analog, phentolamine, and phentolamine related compound A are about 0.84, 1.00, and 1.09, respectively.]

Suitability requirements

Resolution: NLT 2.0 between phentolamine and phentolamine related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution A

Relative standard deviation: NMT 1.0%, Standard solution A

3.4 Analysis

Samples: Standard solution A and Sample solution

Calculate the percentage of the labeled amount of phentolamine mesylate (C₁₇H₁₉N₃O·CH₄O₃S) in the portion of Injection taken:

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

r_U = peak response of phentolamine from the Sample solution

r_S = peak response of phentolamine from Standard solution A

C_S = concentration of USP Phentolamine Mesylate RS in Standard solution A (mg/mL)

C_U = nominal concentration of phentolamine mesylate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-105.0%

4 IMPURITIES

ORGANIC IMPURITIES

Buffer, Solution A, Solution B, Mobile phase, Diluent, Standard solution B, Standard solution C, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.11 µg/mL of USP Phentolamine Mesylate RS in Diluent

Standard solution: 1.2 µg/mL of USP Phentolamine Mesylate RS, 2.8 µg/mL of USP Phentolamine Keto Analog RS from Standard solution C, and 5.2 µg/mL of USP Phentolamine Related Compound A RS from Standard solution B in Diluent

System suitability

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

Suitability requirements

Resolution: NLT 2.0 between phentolamine and phentolamine related compound A, System suitability solution

Relative standard deviation: NMT 5.0% for phentolamine keto analog, phentolamine, and phentolamine related compound A, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phentolamine related compound A and phentolamine keto analog in the portion of Injection taken:

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

r_U = peak response of phentolamine related compound A or phentolamine keto analog from the Sample solution

r_S = peak response of phentolamine related compound A or phentolamine keto analog from the Standard solution

C_S = concentration of USP Phentolamine Related Compound A RS or USP Phentolamine Keto Analog RS in the Standard solution (µg/mL)

C_U = nominal concentration of phentolamine mesylate in the Sample solution (µg/mL)

Calculate the percentage of any unspecified degradation product in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of any unspecified degradation product from the Sample solution

r_S = peak response of phentolamine from the Standard solution

C_S = concentration of USP Phentolamine Mesylate RS in the Standard solution (µg/mL)

C_U = nominal concentration of phentolamine mesylate in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

5 SPECIFIC TESTS

5.1 BACTERIAL ENDOTOXINS TEST (85)

Meets the requirements

5.2 PH (791)

3.5-4.5

5.3 PARTICULATE MATTER IN INJECTIONS (788), Method 1

Meets the requirements

5.4 STERILITY TESTS (71)

Meets the requirements

5.5 OTHER REQUIREMENTS

It meets the requirements in Injections and Implanted Drug Products (1).

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Protect from direct heat and light. Protect from freezing. Store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Phentolamine Keto Analog RS

N-(3-Hydroxyphenyl)-N-(4-tolyl)-4,5-dihydro-1H-imidazole-2-carboxamide.

C₁₇H₁₇N₃O₂ 295.34

USP Phentolamine Mesylate RS

USP Phentolamine Related Compound A RS

N-(2-Aminoethyl)-2-[(3-hydroxyphenyl)(4-tolyl)amino] acetamide.

C₁₇H₂₁N₃O₂ 299.37(USP 1-May-2022)