Gadodiamide Injection
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.
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
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.
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
Chromatographic system
Mode:
LC
Detector:
UV 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)
–35 (system maintained at constant temperature)
Flow rate:
1.5 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.5%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C16H26GdN5O8 in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of gadodiamide from the Sample solution |
| rS | = | = peak response of gadodiamide from the Standard solution |
| CS | = | = concentration of USP Gadodiamide RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of gadodiamide in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
IMPURITIES
Organic Impurities
• Procedure
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 = (rU/rT) × 100
| rU | = | = peak response of each impurity |
| rT | = | = sum of all peaks having a percentage greater than 0.10% |
Acceptance criteria
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
| Name | Acceptance Criteria, NMT (%) |
|---|---|
| Gadodiamide related compound A | 2.0 |
| Gadodiamide related compound B | 2.0 |
| Any other individual impurity | 0.2 |
SPECIFIC TESTS
• Osmolality and Osmolarity, Osmolarity 785:
650–1000 mOsmol/kg
785:
650–1000 mOsmol/kg
• pH 791:
5.5–7.0
791:
5.5–7.0
• Bacterial Endotoxins Test 85:
NMT 0.029 USP Endotoxin Unit/mg of gadodiamide
85:
NMT 0.029 USP Endotoxin Unit/mg of gadodiamide
• Injections 1:
Meets the requirements
1:
Meets the requirements
ADDITIONAL 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.
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
11
USP Endotoxin RS
USP Gadodiamide RS 
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USP Gadodiamide Related Compound A RS
Gadolinium sodium diethylenetriamine pentaacetic acid monomethylamide.
C15H22GdN4NaO9 582.60
Gadolinium sodium diethylenetriamine pentaacetic acid monomethylamide.
C15H22GdN4NaO9 582.60
USP Gadodiamide Related Compound B RS
Gadolinium disodium diethylenetriamine pentaacetic acid.
C14H18GdN3Na2O10 591.54
Gadolinium disodium diethylenetriamine pentaacetic acid.
C14H18GdN3Na2O10 591.54
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3302
Pharmacopeial Forum: Volume No. 36(1) Page 99