Verteporfin for Injection
» Verteporfin for Injection is a sterile mixture of Verteporfin and lipids. It contains not less than 91.0 percent and not more than 110.0 percent of the labeled amount of verteporfin (C41H42N4O8).
Packaging and storage— Preserve in tight Containers for Sterile Solids as described under Injections 1, and store at controlled room temperature, protected from light.
Labeling— The label states that it is to be protected from light after constitution. Label it to indicate that it is intended for intravenous use only; labeling indicates the name and amount of diluent for constitution.
USP Reference standards 11
USP Verteporfin RS Click to View Structure
USP Verteporfin Related Compound A RS Click to View Structure
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
Identification—
A: Ultraviolet Absorption 197U
Solution: 10 µg per mL.
Medium: methanol.
B: The retention times of the two major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
Pyrogen 151: meets the requirements, the test dose being 4 mg per kg.
Sterility 71 It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
Uniformity of dosage units 905: meets the requirements.
Water, Method Ic 921 Use a mixture of methanol and formamide (7:3) as the solvent: not more than 3.0%.
Particulate matter 788: meets the requirements for small-volume injections.
Limit of verteporfin related compound A—
Mobile phase— Prepare as directed in the Assay.
Standard stock solution— Dissolve accurately weighed quantities of USP Verteporfin RS and USP Verteporfin Related Compound A RS in a mixture of acetonitrile and tetrahydrofuran (1:1) to obtain a solution having known concentrations of about 0.167 mg per mL and 6.67 µg per mL, respectively.
Standard solution— Dissolve 3 parts of the Standard stock solution with 2 parts water to obtain a solution having known concentrations of 0.1 mg per mL and 4 µg per mL, respectively. [note—Protect solution from light. ]
Test solution— Use the Assay preparation.
Chromatographic system— The liquid chromatograph is equipped with a 410-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is 1.4 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between the two verteporfin isomeric peaks is not less than 2.5; the tailing factor is not more than 1.3; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of verteporfin related compound A in the portion of Verteporfin for Injection taken by the formula:
20(CS / L)(rU / rS)
in which CS is the concentration, in µg per mL, of USP Verteporfin Related Compound A RS in the Standard solution; L is the labeled quantity, in mg, of verteporfin in Verteporfin for Injection; and rU and rS are the peak responses for verteporfin related compound A in the Test solution and the Standard solution, respectively. Not more than 4.0% is found.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of 1% (w/v) ammonium sulfate solution, acetonitrile, tetrahydrofuran, and acetic acid (20:11:9:2), and adjust with 3.6 M sulfuric acid to a pH of 3.0.
Standard preparation— Dissolve an accurately weighed quantity of USP Verteporfin RS in a mixture of acetonitrile and tetrahydrofuran (1:1) to obtain a solution containing 0.167 mg per mL. Quantitatively dilute this solution with water to obtain a solution having a known concentration of about 0.1 mg per mL. [note—Protect solution from light. ]
Assay preparation— Reconstitute 1 vial of Verteporfin for Injection with deionized water to obtain an approximate concentration of 2 mg per mL, and mix. Quantitatively transfer the contents to a 200-mL volumetric flask, rinsing the vial with a mixture of water, tetrahydrofuran, and acetonitrile (4:3:3), and dilute with a mixture of water, tetrahydrofuran, and acetonitrile (4:3:3) to volume. [note—Protect solution from light. ]
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 410-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is 1.4 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between the peaks for the two verteporfin isomers is not less than 2.5; the tailing factor is not more than 1.3; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses for verteporfin. Calculate the quantity, in mg, of verteporfin (C41H42N4O8) in the portion of Verteporfin for Injection taken by the formula:
200C(rU / rS)
in which C is the concentration, in mg per mL, of USP Verteporfin RS in the Standard preparation; and rU and rS are the sums of the peak responses for the two verteporfin isomeric peaks in the Assay preparation and the Standard preparation, respectively.
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Pharmacopeial Forum: Volume No. 29(3) Page 677