Iopromide Injection
»Iopromide Injection is a sterile solution of Iopromide in Water for Injection.It contains not less than 94.0percent and not more than 105.0percent of the labeled amount of iopromide (C18H24I3N3O8).It may contain small amounts of suitable buffers and of Edetate Calcium Disodium as a stabilizer.It contains no antimicrobial agents.
Packaging and storage— Preserve in single-dose glass Containers for Injectionsas described under Injections á1ñ,and protect from light.Store at controlled room temperature.
Labeling— Label Injection to state that it is not to be used if it contains particulate matter and that after use any unused portion remaining in the container is to be discarded.It is labeled also to state that it is not for intrathecal use.
Identification—
A: Evaporate 3mLof Injection to dryness,and heat the residue so obtained in a crucible in a hood:violet vapors are evolved.
B: The RFvalue of the principal spot in the chromatogram obtained from the Test solution,developed with the Basic eluant,in the test for Ordinary impuritiescorresponds to that obtained from the Standard solutionsimilarly tested.
Bacterial endotoxins á85ñ— It contains not more than 1.25USP Endotoxin Units per mLof Injection.
pHá791ñ: between 6.5and 8.0.
Free iodine— Transfer a volume of Injection,equivalent to 2g of iopromide,to a 50-mLcentrifuge tube.Dilute with water to 24mL.Add 2mLof toluene and 2mLof diluted sulfuric acid solution,and shake:the toluene layer shows no red color.
Limit of free iodide— Transfer 10.0mLof Injection and 50mLof water to a 150-mLtitration vessel,and titrate with 0.001Nsilver nitrate VSusing a silver or platinum electrode in combination with a reference electrode,determining the endpoint potentiometrically.Each mLof 0.001Nsilver nitrate is equivalent to 126.9µg of I.The limit is 80µg of iodide per g of iopromide,based on the labeled content of iopromide.
Limit of free aromatic amine— Proceed as directed in the test for Limit of free aromatic amineunder Iopromide,except to prepare the Test solutionas follows.Transfer an accurately measured volume of Injection,equivalent to about 500mg of iopromide,to a 25-mLvolumetric flask,dilute with water to 20mL,and mix.Calculate the percentage of free aromatic amine based on the labeled amount of iopromide in the Injection taken by the formula:
10(WS/CV)(AU/AS),
in which WSis the quantity,in mg,of USP Iopromide Related Compound A RStaken to prepare the Standard solution;Cis the labeled concentration,in mg per mL,of iopromide in the Injection used to prepare the Test solution;Vis the volume,in mL,of Injection to prepare the Test solution;and AUand ASare the absorbances of the Test solutionand the Standard solution,respectively:not more than 0.2%is found.
Limit of N-acetyl compound (iopromide related compound B)— Using the chromatogram of the Assay preparationobtained in the Assay,calculate the percentage of N-acetyl compound in the iopromide in the Injection taken by the formula:
(WB/C)[(AY1+AY2)/(RY1+RY2)],
in which WBis the quantity,in mg,of USP Iopromide Related Compound B RStaken to prepare the Related compound Bstandard solution;Cis the concentration,in mg of iopromide per mL,in the Assay preparationbased on the labeled amount and the extent of dilution;AY1and AY2are the peak responses for iopromide related compound BY1-and Y2-isomers,respectively,from the Assay preparation;and RY1and RY2are the peak responses for iopromide related compound BY1-and Y2-isomers,respectively,from the Related compound Bstandard solution:not more than 1.5%is found.
Isomer distribution— Using the chromatogram of the Assay preparationobtained in the Assay,calculate the percentage of iopromide isomers in the iopromide in the Injection taken by the formula:
100(ri)/(rE1+rE2+rZ1+rZ2),
in which riis the peak response of each individual iopromide isomer;and rE1,rE2,rZ1,and rZ2,are the peak responses for the iopromide E1-,E2-,Z1-,and Z2-isomers,respectively,from the Assay preparation:between 8.0%and 12.0%of the E1-isomer,between 9.0%and 14.0%of the E2-isomer,between 32.0%and 40.0%of the Z1-isomer,and between 38.0%and 46.0%of the Z2-isomer are found.
Other requirements— It meets the requirements under Injections á1ñ,and meets the requirements for Ordinary impuritiesand Heavy metalsunder Iopromide.
Assay—
Diluent,Mobile phase,Standard preparation,Related compound Bstandard solution,and Chromatographic system— Proceed as directed in the Assayunder Iopromide.
Assay preparation— Dilute an accurately measured volume of Injection,quantitatively and stepwise,with Diluentto obtain a solution having a final nominal concentration of 1.9mg of iopromide per mL.
Procedure— Proceed as directed in the Assayunder Iopromide.Calculate the quantity,in mg,of iopromide (C18H24I3N3O8)in each mLof the Injection taken by the formula:
(CL/D)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Iopromide RSin the Standard preparation;Lis the labeled quantity,in mg,of iopromide in each mLof Injection;Dis the concentration,in mg per mL,of iopromide in the Assay preparation,based on the volume of Injection taken and the extent of dilution;and the other factors are as defined therein.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1050
Pharmacopeial Forum:Volume No.27(2)Page 2170
Phone Number:1-301-816-8305