Gadodiamide Injection
»Gadodiamide Injection is a sterile solution of Gadodiamide in Water for Injection.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of gadodiamide (C16H26GdN5O8).It may contain stabilizers and buffers.Gadodiamide Injection intended for intravascular use contains no antimicrobial agents.
Packaging and storage— Preserve in single-dose Containers for Injectionsas described under Injections á1ñ,of Type Iglass,protected from light.Store at controlled room temperature.
Labeling— Label containers of Injection to direct the user to discard any unused portion.
Identification—
A: Ultraviolet Absorption á197Uñ—
Solution: 57mg of gadodiamide per mL.
Spectral range: 240to 300nm.
Medium: water.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Bacterial endotoxins á85ñ— It contains not more than 0.029USP Endotoxin Unit per mg of gadodiamide.
pHá791ñ: between 5.5and 7.0.
Osmolarity á785ñ: between 650and 1000mOsmol per kg.
Related compounds—
Mobile phase,Postcolumn reagent,System suitability solution,and Chromatographic system— Proceed as directed for Related compoundsunder Gadodiamide.
Test solution— Transfer an accurately measured volume of Injection,equivalent to about 200mg of gadodiamide,to a 100-mLvolumetric flask,dilute with water to volume,and mix.
Procedure— Inject about 10µLof the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.[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.]Calculate the percentage of each impurity in the volume of Injection taken by the formula:
100(ri/rs),
in which riis the peak response of each impurity;and rsis the sum of all peaks having a percentage greater than 0.10%:not more than 2.0%of gadodiamide related compounds Aand Bis found;no individual impurity is more than 0.2%;and the sum of all impurities,other than gadodiamide related compounds Aand B,is not more than 0.5%.
Other requirements— It meets the requirements under Injections á1ñ.
Assay—
Mobile phase,Postcolumn reagent,and Chromatographic system— Proceed as directed in the Assayunder Gadodiamide.
Standard preparation— Transfer about 60mg of USP Gadodiamide RS,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.Transfer 15.0mLof this solution to a 100-mLvolumetric flask,dilute with water to volume,and mix.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 574mg of gadodiamide,to a 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 3.0mLof this solution to a 100-mLvolumetric flask,dilute with water to volume,and mix.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of gadodiamide (C16H26GdN5O8)in each mLof the Injection taken by the formula:
(10,000/3)(C/V)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Gadodiamide RSin the Standard preparation;Vis the volume,in mL,of Injection taken;and rUand rSare the gadodiamide peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 880
Pharmacopeial Forum:Volume No.27(2)Page 2163
Phone Number:1-301-816-8305