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.
• A. Ultraviolet Absorption 197U
Wavelength range: 240300 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.
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
Detector: UV 658 nm
Column: 4.6-mm × 25-cm; 5-µm base-deactivated packing L1. [NoteA second pump mixes the Mobile phase with the Postcolumn reagent prior to detection via a T-junction. ]
Column temperature: 2035 (system maintained at constant temperature)
Flow rate: 1.5 mL/min
Injection size: 10 µL
Sample: Standard solution
Relative standard deviation: NMT 2.5%
Samples: Standard solution and Sample solution
Calculate the percentage of C16H26GdN5O8 in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria: 90.0%110.0%
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
Sample: System suitability solution
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%
[NoteThe 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. ]
Sample: Sample solution
Calculate the percentage of each impurity in the volume of Injection taken:
Result = (rU/rT) × 100
Individual impurity: See Impurity Table 1.
Total impurities: NMT 0.5% of the sum of all impurities other than gadodiamide related compounds A and B
Impurity Table 1
• Osmolality and Osmolarity, Osmolarity 785: 6501000 mOsmol/kg
• pH 791: 5.57.0
• Bacterial Endotoxins Test 85: NMT 0.029 USP Endotoxin Unit/mg of gadodiamide
• Injections 1: Meets the requirements
• Packaging and Storage: Preserve in single-dose or multi-dose plastic or Type I glass containers as described in the section Containers for Injections in Injections 1. Protect from light. Store at controlled room temperature.
• Labeling: Label containers of Injection to direct the user to discard any unused portion.
• USP Reference Standards 11
USP Endotoxin RS
USP Gadodiamide Related Compound A RS
Gadolinium sodium diethylenetriamine pentaacetic acid monomethylamide.
USP Gadodiamide Related Compound B RS
Gadolinium disodium diethylenetriamine pentaacetic acid.
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3302Pharmacopeial Forum: Volume No. 36(1) Page 99