Phentolamine Mesylate

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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C₁₇H₁₉N₃O · CH₄O₃S 377.46

Phenol, 3-[[(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]-, monomethanesulfonate (salt);

m-[N-(2-Imidazolin-2-ylmethyl)-p-toluidino]phenol monomethanesulfonate (salt);

3-{[(4,5-Dihydro-1H-imidazol-2-yl)methyl](4-tolyl)amino}phenol methanesulfonate (USP 1-May-2022) CAS RN®: 65-28-1; UNII: Y7543E5K9T.

1 DEFINITION

Phentolamine Mesylate contains NLT 98.0% and NMT 102.0% of phentolamine mesylate, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M or 197A (USP 1-May-2022)

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 20 μg/mL of Phentolamine Mesylate (USP 1-May-2022) in water

Acceptance criteria: Meets the requirements

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C. The retention time of the major peak of the Sample solution corresponds to that of Standard solution A, as obtained in the Assay. (USP 1-May-2022)

3 ASSAY

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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 to 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: 0.22 mg/mL of Phentolamine Mesylate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 232 nm

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

Flow rate: 1 mL/min

Injection volume: 10 μL

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 0.73%, Standard solution A

Analysis

Samples: Standard solution A and Sample solution

Calculate the percentage of phentolamine mesylate (C₁₇H₁₉N₃O · CH₄O₃S) in the portion of Phentolamine Mesylate taken:

Result = (r_U/r_S) × (C_S/C_U) × 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 = concentration of Phentolamine Mesylate in the Sample solution (mg/mL) (USP 1-May-2022)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Chloride and Sulfate 〈221〉, Sulfate

Sample: 0.10 g of Phentolamine Mesylate

Acceptance criteria: The Sample shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (0.2%).

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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: 0.22 μg/mL of USP Phentolamine Mesylate RS and 0.33 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

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: 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 Phentolamine Mesylate taken:

Result = (r_U/r_S) × (C_S/C_U) × 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 = concentration of Phentolamine Mesylate in the Sample solution (μg/mL)

Calculate the percentage of any unspecified impurity in the portion of Phentolamine Mesylate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecified impurity 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 = 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

Loss on Drying 〈731〉

Analysis: Dry under vacuum at 60° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at 25°, excursions permitted, 15° - 30°.

Change to read:

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 1-May-2022)

USP Phentolamine Mesylate RS

USP Phentolamine Related Compound A RS

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

C₁₇H₂₁N₃O₂ 299.37