Packaging and storage—
Preserve in single-dose glass
Containers for Injections as described under
Injections 
1
, 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 3 mL of Injection to dryness, and heat the residue so obtained in a crucible in a hood: violet vapors are evolved.
B:
The RF value of the principal spot in the chromatogram obtained from the Test solution, developed with the Basic eluant, in the test for Ordinary impurities corresponds to that obtained from the Standard solution similarly tested.
Free iodine—
Transfer a volume of Injection, equivalent to 2 g of iopromide, to a 50-mL centrifuge tube. Dilute with water to 24 mL. Add 2 mL of toluene and 2 mL of diluted sulfuric acid solution, and shake: the toluene layer shows no red color.
Limit of free iodide—
Transfer 10.0 mL of Injection and 50 mL of water to a 150-mL titration vessel, and titrate with 0.001 N silver nitrate VS using a silver or platinum electrode in combination with a reference electrode, determining the endpoint potentiometrically. Each mL of 0.001 N silver nitrate is equivalent to 126.9 µg of I. The limit is 80 µg 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 amine under
Iopromide, except to prepare the
Test solution as follows. Transfer an accurately measured volume of Injection, equivalent to about 500 mg of iopromide, to a 25-mL volumetric flask, dilute with water to 20 mL, 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
WS is the quantity, in mg, of
USP Iopromide Related Compound A RS taken to prepare the
Standard solution; C is the labeled concentration, in mg per mL, of iopromide in the Injection used to prepare the
Test solution; V is the volume, in mL, of Injection to prepare the
Test solution; and
AU and
AS are the absorbances of the
Test solution and 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 preparation obtained 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
WB is the quantity, in mg, of
USP Iopromide Related Compound B RS taken to prepare the
Related compound B standard solution; C is the concentration, in mg of iopromide per mL, in the
Assay preparation based on the labeled amount and the extent of dilution;
AY1 and
AY2 are the peak responses for iopromide related compound B
Y1- and
Y2-isomers, respectively, from the
Assay preparation; and
RY1 and
RY2 are the peak responses for iopromide related compound B
Y1- and
Y2-isomers, respectively, from the
Related compound B standard solution: not more than 1.5% is found.
Isomer distribution—
Using the chromatogram of the
Assay preparation obtained 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
ri is 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 1, and meets the requirements for
Ordinary impurities and
Heavy metals under
Iopromide.
Assay—
Diluent, Mobile phase, Standard preparation, Related compound B standard solution, and Chromatographic system—
Proceed as directed in the
Assay under
Iopromide.
Assay preparation—
Dilute an accurately measured volume of Injection, quantitatively and stepwise, with Diluent to obtain a solution having a final nominal concentration of 1.9 mg of iopromide per mL.
Procedure—
Proceed as directed in the
Assay under
Iopromide. Calculate the quantity, in mg, of iopromide (C
18H
24I
3N
3O
8) in each mL of the Injection taken by the formula:
(CL/D)(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Iopromide RS in the
Standard preparation; L is the labeled quantity, in mg, of iopromide in each mL of Injection;
D is 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.
