Verteporfin for Injection

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

Verteporfin for Injection is a sterile mixture of verteporfin and lipids. It contains NLT 91.0% and NMT 110.0% of the labeled amount of verteporfin (C₄₁H₄₂N₄O₈).

2 IDENTIFICATION

Change to read:

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

Sample solution: 10 µg/mL in methanol

Acceptance criteria: Meets the requirements

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

3 ASSAY

3.1 Procedure

Mobile phase: Acetonitrile, tetrahydrofuran, 1% (w/v) ammonium sulfate solution, and acetic acid (11:9:20:2), adjusted with 3.6 M sulfuric acid to a pH of 3.0

Diluent 1: Acetonitrile and tetrahydrofuran (1:1)

Diluent 2: Acetonitrile, tetrahydrofuran, and water (3:3:4)

Standard solution: 0.1 mg/mL of USP Verteporfin RS prepared as follows. Prepare 0.167 mg/mL of USP Verteporfin RS in Diluent 1, then dilute this solution with water. Protect the solution from light.

Sample solution: Reconstitute 1 vial of Verteporfin for Injection in deionized water to obtain 2 mg/mL of verteporfin. Transfer the contents to a 200-mL volumetric flask, rinsing the vial with Diluent 2. Dilute with Diluent 2 to volume. Protect the solution from light.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV-Vis 410 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1.4 mL/min
• Injection volume: 20 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Resolution: NLT 2.5 between the two verteporfin isomer peaks
• Tailing factor: NMT 1.3
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of verteporfin (C₄₁H₄₂N₄O₈) in the portion of Verteporfin for Injection taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = sum of two verteporfin isomer peak responses from the Sample solution

rₛ = sum of two verteporfin isomer peak responses from the Standard solution

Cₛ = concentration of USP Verteporfin RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of verteporfin in the Sample solution (mg/mL)

Acceptance criteria: 91.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

5.1 Limit of Verteporfin Related Compound A

Mobile phase, Sample solution, Chromatographic system and System suitability: Proceed as directed in the Assay.

Diluent: Acetonitrile and tetrahydrofuran (1:1)

Standard stock solution: 0.167 mg/mL of USP Verteporfin RS and 6.67 µg/mL of USP Verteporfin Related Compound A RS in Diluent

Standard solution: 0.1 mg/mL of USP Verteporfin RS and 4 µg/mL of USP Verteporfin Related Compound A RS prepared as follows. Dissolve 3 parts of the Standard stock solution with 2 parts of water. Protect the solution from light.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV-Vis 410 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1.4 mL/min
• Injection volume: Equal volumes for Standard solution and Sample solution

System suitability

• Sample: Standard solution
• Suitability requirements
• Resolution: NLT 2.5 between the two verteporfin isomer peaks
• Tailing factor: NMT 1.3
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of verteporfin related compound A in the portion of Verteporfin for Injection taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of verteporfin related compound A from the Sample solution

rₛ = peak response of verteporfin related compound A from the Standard solution

Cₛ = concentration of USP Verteporfin Related Compound A RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of verteporfin in the Sample solution (mg/mL)

Acceptance criteria: NMT 4.0%

6 SPECIFIC TESTS

6.1 Pyrogen Test 〈151〉

Test dose: 4 mg/kg

Acceptance criteria: Meets the requirements

6.2 Sterility Tests 〈71〉

It meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined, Membrane Filtration.

6.3 Water Determination, Method Ic 〈921〉

NMT 3.0%, use a mixture of methanol and formamide (7:3) as the solvent.

6.4 Particulate Matter in Injections 〈788〉

Meets the requirements for small-volume injections

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution, and store at controlled room temperature, protected from light.

Labeling: The label states that it is to be protected from light after constitution, indicates that it is intended for intravenous use only, and includes the name and amount of diluent for constitution.

USP Reference Standards 〈11〉

USP Verteporfin RS

USP Verteporfin Related Compound A RS

trans-(±)-18-Ethenyl-4,4a-dihydro-3,4-bis(methoxycarbonyl)-4a,8,14,19-tetramethyl-23H,25H-benzo[b]porphine-9,13-dipropionic acid.

C₄₀H₄₀N₄O₈ 704.77