Gadodiamide 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

Gadodiamide Injection is a sterile solution of Gadodiamide in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of gadodiamide (C₁₆H₂₆GdN₅O₈). It may contain stabilizers and buffers. Gadodiamide Injection intended for intravascular use contains no antimicrobial agents.

2 IDENTIFICATION

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

Wavelength range: 240–300 nm

Solution: 57 mg/mL of gadodiamide in water

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

Procedure

Solution A: Dissolve 14 mL of triethylamine and 5.7 mL of glacial acetic acid in 1 L of water.

Mobile phase: Transfer 50 mL of Solution A to a 1-L volumetric flask. Add 900 mL of water. Adjust with 1 N acetic acid or 1 N sodium hydroxide to a pH between 6.5 and 7.0. Dilute with water to volume.

Postcolumn reagent: Dissolve 325 mg of Urea in a solution of 60 mg of arsenazo III acid in 550 mL of water previously acidified with 3.2 mL of nitric acid. Pass the solution through a filter of 0.45-µm pore size, wash the filter with 400 mL of water, and dilute with water to 1000 mL. Standard solution: 0.18 mg/mL of USP Gadodiamide RS

Sample solution: Equivalent to a nominal concentration of 0.18 mg/mL of gadodiamide from Injection

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Vis 658 nm

Column: 4.6-mm × 25-cm; 5-µm base-deactivated packing L1. [Note—A second pump mixes the Mobile phase with the Postcolumn reagent prior to detection via a T-junction.]

Column temperature: 20°–35° (system maintained at constant temperature)

Flow rate: 1.5 mL/min

Injection volume: 10 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.5%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of gadodiamide (C₁₆H₂₆GdN₅O₈) in the portion of Injection taken:

Result = (r_U /r_S ) × (C_S /C_U) × 100

r_U = peak response of gadodiamide from the Sample solution

r_S = peak response of gadodiamide from the Standard solution

C_S = concentration of USP Gadodiamide RS in the Standard solution (mg/mL)

C_U = nominal concentration of gadodiamide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Organic Impurities

Solution A, Mobile phase, and Chromatographic system: Prepare as directed in the Assay.

Postcolumn reagent: Dissolve 120 mg of arsenazo III acid in 400 mL of water previously acidified with 6.3 mL of nitric acid. Add 650 mg of urea, and mix to dissolve. Pass the solution through a filter of 0.45-µm pore size, washing the filter with 600 mL of water. Dilute with water to 1000 mL.

System suitability solution: 10 µg/mL of USP Gadodiamide Related Compound A RS, 10 µg/mL of USP Gadodiamide Related Compound B RS, and 2 mg/mL of USP Gadodiamide RS in an aqueous solution

Sample solution: Equivalent to a nominal concentration of 2 mg/mL of gadodiamide from Injection

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.0 between the gadodiamide and gadodiamide related compound A peaks; NLT 1.5 between gadodiamide related compound A and gadodiamide related compound B peaks

Relative standard deviation: NMT 10%

[Note—The tail of the gadodiamide peak may contain a small shoulder due to an isomer. The area of the shoulder should be included in the gadodiamide peak area.]

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the volume of Injection taken:

Result = (r_U /r_T ) × 100

r_U = peak response of each impurity

r_T = sum of all peaks having a percentage greater than 0.10%

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

Change to read:

Osmolality and Osmolarity 〈785〉

Osmolality: (Oficial 1-Aug-2022) 650–1000 mOsmol/kg

pH 〈791〉: 5.5–7.0

Bacterial Endotoxins Test 〈85〉: NMT 0.029 USP Endotoxin Unit/mg of gadodiamide

Injections and Implanted Drug Products 〈1〉: Meets the requirements

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose plastic or Type I glass containers. Store at controlled room temperature, protected from light. Do not freeze.

Labeling: Label containers of Injection to direct the user to discard any unused portion. Label it to state its routes of administration. Label it to indicate “serious injury can occur if given by intrathecal route.”

USP Reference Standards 〈11〉

USP Gadodiamide RS

USP Gadodiamide Related Compound A RS

Gadolinium sodium diethylenetriamine pentaacetic acid monomethylamide.

C₁₅H₂₂GdN₄NaO₉                582.60

USP Gadodiamide Related Compound B RS

Gadolinium disodium diethylenetriamine pentaacetic acid.

C₁₄H₁₈GdN₃Na₂O₁₀         591.54