Gadoterate Meglumine 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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C₁₆H₂₅GdN₄O₈ · C₇H₁₇NO₅                753.86

d-Glucitol, 1-deoxy-1-(methylamino)-, [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetato(4-)-

κN¹,κN⁴,κN⁷,κN¹⁰,κO¹,κO⁴,κO⁷,κO¹⁰]gadolinate(1-) (1:1);

1-Deoxy-1-(methylamino)-d-glucitol hydrogen [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetato(4-)-

κN¹,κN⁴,κN⁷,κN¹⁰,κO¹,κO⁴,κO⁷,κO¹⁰]gadolinate(1-) CAS RN®: 92943-93-6.

1 DEFINITION

Gadoterate Meglumine Injection is a sterile solution of Gadoterate Meglumine in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of gadoterate meglumine (C₁₆H₂₅GdN₄O₈ · C₇H₁₇NO₅  ).

2 IDENTIFICATION

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

Analytical wavelength: 265–285 nm

Sample solution: Dilute Injection with water (1:10).

Acceptance criteria: The absorption spectrum exhibits maxima at 273 and 276 nm.

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

Buffer 1: 5.5 g/L of ammonium acetate. Adjust with acetic acid to a pH of 6.0.

Buffer 2: 2.1 g/L of ammonium acetate. Adjust with acetic acid to a pH of 6.0.

Mobile phase: Acetonitrile and Buffer 1 (65:35)

Diluent: Acetonitrile and Buffer 2 (60:40)

Standard solution: 3.6 mg/mL of USP Gadoterate Meglumine RS in Diluent. Vigorous shaking may be required for complete dissolution. Sample solution: Nominally 3.6 mg/mL of gadoterate meglumine from a suitable volume of Injection in Diluent. Vigorous shaking may be required for complete dissolution.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Fluorescence

Excitation wavelength: 274 nm

Emission wavelength: 312 nm

Column: 4.6-mm × 25.0-cm; 5-µm packing L114

Column temperature: 50°

Flow rate: 0.8 mL/min

Injection volume: 5 µL

Run time: NLT 2.5 times the retention time of gadoterate

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 1.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of gadoterate meglumine (C₁₆H₂₅GdN₄O₈ · C₇H₁₇NO₅) in the portion of Injection taken:

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

r_U = peak response of fluorescence emission for gadoterate from the Sample solution

r_S = peak response of fluorescence emission for gadoterate from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

Change to read:

Content of Meglumine

Sample solution: Gadoterate Meglumine Injection

Blank: Water

Instrumental conditions

Mode: Polarimetry (see Optical Rotation 〈781S〉, Procedures, Specic Rotation), except for Temperature

Temperature: 20°

Lamp: Sodium

Analytical wavelength: 589 nm

Cell: 1 dm

Analysis:

Samples: Sample solution and Blank

Determine the angular rotation (see Optical Rotation 〈781〉).

Calculate the amount of meglumine as a percentage of the formulation content of meglumine (C₇H₁₇NO₅) in the portion of Injection 7 17 5

taken:

Result = (a/α) × 100 _{(ERR 1-Jun-2021)} × (1/l) × (1/L) × 100

a = observed angular rotation of the Sample solution corrected for the Blank (°)

α = average specific rotation of meglumine, 24.0 deg · dm⁻¹ · g⁻¹ · dL

l = cell path length, dm

L = formulation content of meglumine in the Injection, 9.76 g/dL

Acceptance criteria: 90.0%–110.0%

5 IMPURITIES

5.1 Limit of Free Gadolinium

Buffer: 5.7 mL/L of glacial acetic acid and 8.2 g/L of sodium acetate (10:20). [Note—If necessary, adjust with 5.7 mL/L of glacial acetic acid or 8.2 g/L of sodium acetate to a pH between 4.8 and 5.2.]

Indicator solution: 0.1% xylenol orange in water

Sample solution: Transfer 20 mL of Injection into a suitable ask. Add 30 mL of water, 10 mL of Buffer, 1 drop of pyridine, and 5–10 drops of Indicator solution.

Blank: Water

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.01 M edetate disodium VS

Endpoint detection: Visual

Analysis

Sample: Sample solution

Titrate with Titrant to a yellow endpoint. Add an additional drop of pyridine. If a violet color appears, continue the analysis until it turns yellow.

Calculate the percentage of free gadolinium (% w/v) in the portion of Injection taken:

Result = [V_T × M × F × (1/V_U)] × (1/10)

V_T = volume of Titrant consumed (mL)

M = molarity of Titrant (mM/mL)

F = equivalency factor, 157.25 mg/mM

V_U = volume of Injection used to prepare the Sample solution, 20 mL

Acceptance criteria: NMT 0.001% (w/v)

5.2 Limit of Free Tetraxetan

Buffer 1: 5.7 mL/L of glacial acetic acid and 8.2 g/L of sodium acetate (10:20). [Note—If necessary, adjust with 5.7 mL/L of glacial acetic acid or 8.2 g/L of sodium acetate to a pH between 4.8 and 5.2.]

Buffer 2: 0.5 g/L of copper sulfate in water

Sample solution: Transfer 5 mL of Injection into a suitable ask. Add 5 mL each of Buffer 1 and Buffer 2.

Blank: Transfer 5 mL of water into a suitable ask. Add 5 mL each of Buffer 1 and Buffer 2.

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.002 M edetate disodium VS

Endpoint detection: Potentiometric. [Note—An electrode system consisting of a copper indicator electrode and a calomel reference electrode is recommended.]

Analysis

Samples: Sample solution and Blank

Titrate potentiometrically with Titrant.

Calculate the percentage of free tetraxetan (% w/v) in the portion of Injection taken:

Result = [(V_B − V_T ) × M × F] × (1/V_U ) × (1/10)

V_B = volume of Titrant consumed by the Blank (mL)

V_T = volume of Titrant consumed by the Sample solution (mL)

M = actual molarity of Titrant (mM/mL)

F = equivalency factor, 404.42 mg/mM

V_U = volume of Injection used to prepare the Sample solution, 5 mL

Acceptance criteria: 0.005%–0.05% (w/v)

6 SPECIFIC TESTS

pH 〈791〉: 6.5–8.0

Particulate Matter in Injections 〈788〉: It meets the requirements for small-volume injections.

Sterility Tests 〈71〉: Meets the requirements

Bacterial Endotoxins Test 〈85〉: Meets the requirements

Container Content for Injections 〈697〉: Meets the requirements

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Gadoterate Meglumine RS.