»Ioversol contains not less than 97.0percent and not more than 101.0percent of C18H24I3N3O9,calculated on the anhydrous basis.
Packaging and storage Preserve in well-closed containers.Store at 25,excursions permitted between 15and 30.
USP Reference standards á11ñ USP Ioversol RS.USP Ioversol Related Compound A RS.USP Ioversol Related Compound B RS.
B: Heat about 500mg in a crucible:violet vapors are evolved.
Water,Method Iá921ñ: not more than 5%.
Residue on ignition á281ñ: not more than 0.1%.
Mobile phase Prepare a degassed mixture of water and acetonitrile (99.5:0.5).
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 about 1.0µg per mLof USP Ioversol Related Compound A RSand 5.0µg per mLof USP Ioversol Related Compound B RS.
Test solution Transfer about 100mg of Ioversol,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.
Chromatographic system(see Chromatography á621ñ) The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×25-cm stainless steel column containing packing L7.The column temperature is maintained at 35±0.5.The system is capable of operating at a column pressure of up to 3000psi.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the resolution,R,between ioversol related compound Aand ioversol related compound Bis not less than 2.0;and the relative standard deviation for replicate injections is not more than 5%.
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 portion of Ioversol taken by the formula:
100(C/W)(rU/rS),in which Cis the concentration,in mg per mL,of USP Ioversol Related Compound A RSor USP Ioversol Related Compound B RSin the Standard solution;Wis the concentration,in mg per mL,of Ioversol in the Test solution;rUis the peak response obtained from the Test solution;and rSis the average peak response from the Standard solution.Not more than 0.10%of ioversol related compound Aand not more than 0.50%of ioversol related compound Bare found.
Iodine and iodide Dissolve 2.0g of Ioversol in water in a 50-mLglass-stoppered cylinder,and dilute with water to 15mL.To this solution add 5mLeach of diluted sulfuric acid and toluene.Shake vigorously,and allow the layers to separate:the toluene layer shows no red color.Add 1mLof sodium nitrite solution (1in 50),and shake:any red color in the toluene layer is not darker than that obtained from a mixture of 2mLof potassium iodide solution (1in 4000)and 13mLof water,similarly treated (0.02%of iodide).
Heavy metals,Method Iá231ñ: 0.002%.
Standard solution Into a 50-mLcolor-comparison tube,pipet 2mLof Standard Lead Solution(20µg of lead),and dilute with water to 10mL.
Test solution Dissolve 1g in 10mLof water in a 50-mLcolor-comparison tube.
Procedure For each of the tubes containing the Standard solutionand the Test solution,adjust with 1Nacetic acid or 6Nammonium hydroxide to a pHof 3.0to 4.0using short-range pHindicator paper as external indicator,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.
Assay Transfer about 500mg of Ioversol,accurately weighed,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
USP28NF23Page 1054Pharmacopeial Forum:Volume No.29(6)Page 1910