Verteporfin

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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C₄₁H₄₂N₄O₈ 718.79

23H,25H-Benzo[b]porphine-9,13-dipropanoic acid, 18-ethenyl-4,4a-dihydro-3,4-bis(methoxycarbonyl)-4a,8,14,19-tetramethyl-, monomethyl ester, trans-;

(±)-trans-3,4-Dicarboxy-4,4a-dihydro-4a,8,14,19-tetramethyl-18-vinyl-23H,25H-benzo[b]porphine-9,13-dipropanoic acid, 3,4,9-trimethyl ester mixture with (±)-trans-3,4-dicarboxy-4,4a-dihydro-4a,8,14,19-tetramethyl-18-vinyl-23H,25H-benzo[b]porphine-9,13-dipropionic acid, 3,4,13-trimethyl ester CAS RN®: 129497-78-5; UNII: 0X9PA28K43.

1 DEFINITION

Verteporfin contains NLT 94.0% and NMT 102.0% of verteporfin (C₄₁H₄₂N₄O₈), calculated on the anhydrous basis.

[Caution-Verteporfin is a light-activated drug used in photodynamic therapy. Care should be taken to avoid contact with eyes and skin.]

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M

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

3.1 Procedure

Solution A: Acetonitrile, 1% (w/v) aqueous ammonium sulfate, glacial acetic acid, and 3.6 M sulfuric acid (10:10:1:0.027)

Solution B: Tetrahydrofuran, 1% (w/v) aqueous ammonium sulfate, glacial acetic acid, and 3.6 M sulfuric acid (10:10:1:0.034)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and tetrahydrofuran (1:1)

Standard solution: 0.25 mg/mL of USP Verteporfin RS prepared as follows. Transfer USP Verteporfin RS to a suitable volumetric flask, add Diluent equivalent to 60% of the flask volume and dissolve, then dilute with water to volume. Protect this solution from light.

Sample solution: Equivalent to 0.25 mg/mL of Verteporfin prepared as follows. Transfer 25 mg of Verteporfin to a 100-mL volumetric flask, add 60 mL of Diluent and dissolve, then dilute with water to volume. Protect this solution from light.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: Vis 410 nm
• Column: 4.6-mm × 25-cm; packing L1
• Column temperature: 30°
• Flow rate: 1.5 mL/min
• Injection volume: 20 µL

System suitability

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of verteporfin (C₄₁H₄₂N₄O₈) in the portion of Verteporfin taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

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

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

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

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

Calculate the ratio for the two verteporfin regioisomer peaks from the Sample solution.

Acceptance criteria

• Assay: 94.0%–102.0% on the anhydrous basis
• Peak ratio: 0.9–1.1

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.2%

4.2 Organic Impurities

Procedure

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

Sensitivity solution: 0.25 µg/mL of USP Verteporfin RS in water from the Standard solution

System suitability

• Samples: Standard solution and Sensitivity solution
• Suitability requirements
• Signal-to-noise ratio: NLT 10, Sensitivity solution
• Resolution: NLT 2.5 between the two verteporfin peaks, Standard solution
• Tailing factor: NMT 1.3, Standard solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Sample: Sample solution

Calculate the percentage of each individual impurity in the portion of Verteporfin taken:

Result = (rᵤ/rₜ) × 100

rᵤ = peak response for each impurity from the Sample solution

rₜ = sum of the responses of all the peaks from the Sample solution

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 10² cfu/g.

Bacterial Endotoxins Test 〈85〉: NMT 0.5 USP Endotoxin Unit/mg of verteporfin

Water Determination, Method Ic 〈921〉: NMT 1.4%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store in a freezer.

USP Reference Standards 〈11〉

USP Verteporfin RS