Technetium Tc 99m Disofenin Injection
»Technetium Tc 99m Disofenin Injection is a sterile,aqueous solution,suitable for intravenous administration,of disofenin that is labeled with 99mTc.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 99mTc as a disofenin complex,expressed in megabecquerels (microcuries or millicuries)per mLat the time indicated on the labeling.It contains a suitable reducing agent.
Packaging and storage— Preserve in single-dose or in multiple-dose containers sealed under a suitable inert atmosphere.
Labeling— Label it to include the following,in addition to the information specified for Labelingunder Injections á1ñ:the time and date of preparation;the amount of 99mTc as expressed as total megabecquerels (microcuries or millicuries)and concentration as megabecquerels (microcuries or millicuries)per mLat the time of preparation;the expiration date and time;and a statement “Caution—Radioactive Material.”The labeling indicates that in making dosage calculations,correction is to be made for radioactive decay,and also indicates that the radioactive half-life of 99mTc is 6.0hours.
pHá791ñ: between 4.0and 5.0.
Radiochemical purity— The determination of radiochemical purity for this Injection requires the use of two separate chromatography systems.
System A— Apply a measured volume of Injection,appropriately diluted,such that it provides a count rate of about 20,000counts per minute,about 13mm from one end of a 10-×51-mm thin-layer chromatographic strip impregnated with silica gel (see Chromatography á621ñ),and immediately develop the chromatogram over a suitable period by ascending chromatography,using methanol as the solvent.Allow the chromatogram to dry.Cut the chromatogram in two along a line about 13mm from the top.Place the top and bottom strips into separate counting containers.Determine the radioactivity of each,using a suitable ionization chamber.Hydrolyzed Tc 99m and technetium-tin colloid are located at the origin of the bottom strip (RF0to 0.1).
System B— Pretreat a 1.3-×51-mm strip of chromatographic paper by soaking it for 1minute in a 0.3Mcarbonate-bicarbonate buffer,pH9.0,prepared by dissolving 0.3g of anhydrous sodium carbonate and 1.9g of anhydrous sodium bicarbonate in 100mLof water.Remove the paper strip,blot lightly with absorbent paper,and dry in an oven for about 45minutes at 85.Proceed as directed for System Ausing the pretreated chromatographic paper and a developing solvent of methyl ethyl ketone.Free pertechnetate is located at the solvent front (top strip).The sum of the percentage of radioactivity at the origin in System Aand the percentage of radioactivity at the solvent front in System Bis not greater than 10.0%.
Biological distribution— Inject between 75MBq and 111MBq (2mCi and 3mCi)of Injection,in a volume not exceeding 0.1mL,into the caudal vein of each of three 25-to 40-g male albino mice.One hour after the injection,anesthetize and then decapitate the animals.Drain the blood of each separately into pre-weighed counting containers.Dissect the animals,and place the kidneys,liver,stomach (exclusive of duodenum),and gallbladder,and intestines,of each mouse into separate counting containers.Using a suitable counting assembly,determine the radioactivity of each container.Correct all radioactivity measurements for decay.Determine the percentage of radioactivity in the kidneys,liver,stomach,and gallbladder and intestines taken by the formula:
100(A/B),
in which Ais the radioactivity,in counts per minute,in the organ,and Bis the total radioactivity,in counts per minute,injected.Determine the percentage of radioactivity in the blood taken by the formula:
[100(C/WS)0.07(WR)]/B,
in which Cis the radioactivity,in counts per minute,in the specimen of blood,WSis the weight,in g,of the blood specimen,0.07is the assumption that the total blood weight of the mouse is 7%of the total body weight,and WRis the weight,in g,of the mouse.Not less than 70%of the injected radioactivity is present in the gallbladder and intestines,not more than 10.0%of the injected radioactivity is present in the liver,not more than 10.0%of the injected radioactivity is present in the kidneys,not more than 3.0%of the injected radioactivity is present in the stomach,and not more than 3.0%of the injected radioactivity is present in the blood,in not less than two mice.
Other requirements— It meets the requirements of the tests for Radionuclide identification,Radionuclidic purity,and Bacterial endotoxinsunder Sodium Pertechnetate Tc 99m Injection.It also meets the requirements under Injections á1ñ,except that it may be distributed or dispensed prior to completion of the test for Sterility,the latter test being started on the date of preparation,and except that it is not subject to the recommendation on Volume in Container.
Assay for radioactivity á821ñ— Using a suitable counting assembly (see Selection of a Counting Assembly),determine the radioactivity,in MBq (µCi or mCi)per mL,of Injection by the use of a calibrated system.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(RMI)Radiopharmaceuticals and Medical Imaging Agents
USP28–NF23Page 1854
Phone Number:1-301-816-8305