Ioversol Injection
»Ioversol Injection is a sterile solution of Ioversol in Water for Injection.It contains not less than 95.0percent and not more than 105.0percent of the labeled amounts of ioversol (C18H24I3N3O9)and iodine (I).It may contain small amounts of suitable buffers and Edetate Calcium Disodium as a stabilizer.Ioversol Injection intended for intravascular use contains no antimicrobial agents.
Packaging and storage— Preserve in single-dose containers,preferably of Type Iglass,protected from light.
Labeling— Label containers of Injection intended for intravascular injection to direct the user to discard any unused portion remaining in the container.
Identification—
A: The IRabsorption spectrum of the test specimen,a zinc sulfide cell having a thickness of 0.01to 0.02mm being used,exhibits maxima only at the same wavelength as that of a similar preparation of USP Ioversol RS.
B: Heat about 1mLin a crucible:violet vapors are evolved.
Bacterial endotoxins á85ñ— It contains not more than 1.4USP Endotoxin Units per mLof Injection.
pHá791ñ: between 6.0and 7.4.
Heavy metals,Method Iá231ñ—
Standard solution— Into a 50-mLcolor-comparison tube pipet 2mLof Standard Lead Solution(20µg of Pb),and dilute with water to 5mL.
Test solution— Into a 50-mLcolor-comparison tube,pipet a volume of Injection,equivalent to 1g of ioversol,and dilute with water to 5mL.
Procedure— For each of the tubes containing the Standard solutionand the Test solution,adjust with 1Nacetic acid or 6Nammonium hydroxide to a pHbetween 3.0and 4.0,using short-range pHindicator paper as external indicator.Add 5.0mLof ferrous sulfate solution (1in 1000),dilute with water to 40mL,and mix.Add 1.2mLof thioacetamide-glycerin base TSand 2mLof pH3.5Acetate Buffer,allow to stand for 5minutes,and view downward over a white surface:the color of the solution from the Test solutionis not darker than that of the solution from the Standard solution,treated in the same manner.The limit is 20µg per g.
Other requirements— It meets the requirements under Injections á1ñ.
Related compounds—
Mobile phase and Chromatographic system—Proceed as directed in the test for Related compoundsunder Ioversol.
Standard solution— Dissolve accurately weighed quantities of USP Ioversol Related Compound A RSand USP Ioversol Related Compound B RSin water to obtain a solution having known concentrations of 1.5and 15µg per mL,respectively.
Test solution— Dilute an accurately measured volume of Injection with water to obtain a solution containing 1mg of ioversol per mL.
Procedure— Separately inject equal volumes (about 50µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the percentage of each ioversol related compound in the volume of Injection taken by the formula:
100(CS/CU)(rU/rS),
in which CSis the concentration,in mg per mL,of USP Ioversol Related Compound A RSor USP Ioversol Related Compound B RSin the Standard solution,CUis the concentration,in mg per mL,of Ioversol in the Assay preparation,rUis the peak response obtained from the Test solution,and rSis the average peak response obtained from the Standard solution.Not more than 0.15%of ioversol related compound Aand not more than 1.5%of ioversol related compound Bare found.
Assay— Transfer an accurately measured volume of Injection,equivalent to about 0.5g of ioversol,to a glass-stoppered,125-mLconical flask,add 12mLof 5Nsodium hydroxide,20mLof water,and 1g of powdered zinc,connect the flask to a reflux condenser,and reflux for 30minutes.Cool the flask to room temperature,rinse the condenser with 20mLof water,disconnect the flask from the condenser,and filter the mixture.Rinse the flask and filter thoroughly,adding the rinsings to the filtrate.Add 40mLof 2Nsulfuric acid,and titrate immediately with 0.05Nsilver nitrate VS,determining the endpoint potentiometrically,using a silver-silver chloride double junction reference electrode and a silver billet electrode.Each mLof 0.05Nsilver nitrate is equivalent to 13.45mg of C18H24I3N3O9.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1054
Phone Number:1-301-816-8305