Indocyanine Green 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

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Indocyanine Green for Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of indocyanine green (USP 1-Aug-2022) (C₄₃H₄₇N₂NaO₆S₂).

2 IDENTIFICATION

2.1 A. IDENTIFICATION TESTS-GENERAL (19)〉, Chemical Identification Tests, Sodium and Sulfate

Analysis: Incinerate a portion of Indocyanine Green for Injection and use the residue.

Acceptance criteria: Meets the requirements

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2.2 B.

Sample solution: 0.05 mg/mL of indocyanine green from Indocyanine Green for Injection in water

Analysis: Add 10 drops of sodium hydroxide TS (USP 1-Aug-2022) to the Sample solution and heat to about 60°. Add 10 drops of Hydrogen peroxide TS and mix.

Acceptance criteria: A red color develops within 4 min, which on standing, fades to a pale orange.

3 ASSAY

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3.1 PROCEDURE

Standard solution: 2 µg/mL of USP Indocyanine Green RS in methanol

Sample solution: Nominally 2 µg/mL of indocyanine green from Indocyanine Green for Injection in methanol

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.) (USP 1-Aug-2022)

Mode: UV-Vis

Analytical wavelength: 785 nm

Cell: 1 cm

Blank: Methanol

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of indocyanine green (C₄₃H₄₇N₂NaO₆S₂) in the portion of Indocyanine Green for Injection taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Indocyanine Green RS in the Standard solution (µg/mL)

C_U = nominal concentration of indocyanine green in the Sample solution (µg/mL)

Acceptance criteria: 90.0%-110.0%

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4 OTHER COMPONENTS

4.1 SODIUM IODIDE

Sample: Nominally 200 mg of indocyanine green from Indocyanine Green for Injection

Titrimetric system

Mode: Direct titration

Titrant: 0.01 N silver nitrate VS

Electrode system: Silver-glass

Endpoint detection: Potentiometric

Analysis: Dissolve the Sample in 100 mL of water. Add 1 mL of nitric acid and mix. Titrate with Titrant to a potentiometric endpoint.

Calculate the percentage of sodium iodide (NaI) in the portion of Indocyanine Green for Injection taken:

Result = [(V × N × F) / W] × 100

V = volume of Titrant consumed by the Sample (mL)

N = Titrant concentration, in normality (mEq/mL)

F = equivalency factor of sodium iodide, 149.9 mg/mEq

W = nominal weight of indocyanine green in the Sample taken (mg)

Acceptance criteria: NMT 5.0% on the dried basis (USP 1-Aug-2022)

5 PERFORMANCE TESTS

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5.1 UNIFORMITY OF DOSAGE UNITS (USP 1-AUG-2022)

Standard solution and Instrumental conditions: Proceed as directed in the Assay.

Sample stock solution: Individually transfer the contents of each of 5 containers of Indocyanine Green for Injection to separate 100-mL volumetric flasks with the aid of methanol and dilute with methanol to volume.

Sample solution: Nominally 2.5 µg/mL of indocyanine green from the Sample stock solution in methanol

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the label claim of indocyanine green (C₄₃H₄₇N₂NaO₆S₂) in each container of Indocyanine Green for Injection taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Indocyanine Green RS in the Standard solution (µg/mL)

C_U = nominal concentration of indocyanine green in the Sample solution (µg/mL)

Acceptance criteria: The requirements are met if the content is 85%–115% of label claim in NLT 4 of the containers and is 75%-125% of label claim in all 5 containers. (USP 1-Aug-2022)

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6 IMPURITIES

ARSENIC (211), Procedures, Method II: NMT 8 ppm

LEAD (251):

Sample solution: A 5-mL portion of the solution prepared for the test for Arsenic 〈211〉, Procedures, Method II

Analysis: Proceed as directed for the limit test of Lead 〈251〉. Use 3 mL of Ammonium Citrate Solution, 1 mL of Potassium Cyanide Solution, and 0.5 mL of Hydroxylamine Hydrochloride Solution.

Acceptance criteria: NMT 10 ppm (USP 1-Aug-2022)

7 SPECIFIC TESTS

CONSTITUTED SOLUTION: At the time of use, it meets the requirements for Injections and Implanted Drug Products (1), Product Quality Tests

Common to Parenteral Dosage Forms, Specific Tests, Completeness and Clarity of Solutions.

STERILITY TESTS (71): Meets the requirements

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BACTERIAL ENDOTOXINS TEST (85): Meets the requirements (USP 1-Aug-2022)

PH (791)

Sample solution: 5 mg/mL of Indocyanine Green for Injection in water

Acceptance criteria: 5.5-7.5

OTHER REQUIREMENTS: It meets the requirements in Labeling (7), Labels and Labeling for Injectable Products.

8 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve as described in Packaging and Storage Requirements (659), Injection Packaging, Packaging for Constitution.

USP REFERENCE STANDARDS (11)

USP Indocyanine Green RS