Thallous Chloride Tl 201Injection
»Thallous Chloride Tl 201Injection is a sterile,isotonic,aqueous solution of radioactive thallium (201Tl)in the form of thallous chloride suitable for intravenous administration.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 201Tl as chloride,expressed in megabecquerels (microcuries or millicuries)per mL,at the time indicated in the labeling.Other chemical forms of radioactivity do not exceed 5.0percent of the total radioactivity.It may contain a preservative or stabilizer.
Packaging and storage— Preserve in single-dose or multiple-dose containers.
Labeling— Label it to include the following,in addition to the information specified for Labelingunder Injections á1ñ:the time and date of calibration;the amount of 201Tl as labeled thallous chloride expressed as total megabecquerels (microcuries or millicuries)and concentration as megabecquerels (microcuries or millicuries)per mLat the time of calibration;the expiration date and time;and the 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 201Tl is 73.1hours.
Radionuclide identification (see Radioactivity á821ñ)— Its gamma-ray spectrum is identical to that of a specimen of 201Tl of known purity that exhibits a major photopeak at an energy of 167KeVand a minor photopeak of 135KeV.
Bacterial endotoxins á85ñ— The limit of endotoxin content is not more than 175/VUSP Endotoxin Unit per mLof the Injection,when compared with the USP Endotoxin RS,in which Vis the maximum recommended total dose,in mL,at the expiration date or time.
pHá791ñ: between 4.5and 7.5.
Radiochemical purity— Soak a 2.5-×15.0-cm cellulose polyacetate strip in 0.05Medetate disodium for 45to 60minutes.Remove the strip with forceps,taking care to handle the outer edges only.Place the strip between two absorbent pads,and blot to remove excess solution.Apply not less than 5µLof a previously mixed solution consisting of equal volumes of Injection and 0.05Medetate disodium to the center of the blotted strip,and mark the point of application.Attach the strip to the support bridge of an electrophoresis chamber containing equal portions of 0.05Medetate disodium in each side of the chamber.Ensure that each end of the strip is in contact with the 0.05Medetate disodium.Attach the chamber cover,and perform the electrophoresis at 250volts for 30minutes.Remove the strip from the chamber,and allow to air-dry without blotting.Using a suitable scanner and counting assembly,determine the radioactivity.Not less than 95.0%of the radioactivity on the strip migrates toward the cathode as a single peak.
Radionuclidic purity— Using a suitable counting assembly (see Selection of a Counting Assemblyunder Radioactivity á821ñ),determine the radioactivity of each radionuclidic impurity in the Injection by use of a calibrated system.Not less than 95.0%of the total radioactivity is present as thallium 201.In addition,not more than 2.0%of thallium 200(half-life is 26.1hours),not more than 0.3%of lead 203(half-life is 52.02hours),and not more than 2.7%of thallium 202(half-life is 12.23days)are present.
Content of thallium—
Standard thallium solution— Transfer 235mg of thallous chloride,accurately weighed,to a 1000-mLvolumetric flask,dilute with water to volume,and mix.Transfer 1.0mLof the resulting solution to a 100-mLvolumetric flask,dilute with saline TScontaining 0.9%benzyl alcohol to volume,and mix.This standard solution contains 2µg of thallium per mL.
Procedure— Transfer 1.0-mLportions of the Standard thallium solutionand the Injection to separate screw-cap test tubes.To each tube add 2drops of a solution,prepared by carefully mixing 18mLof nitric acid and 82mLof hydrochloric acid,and mix.Then add to each tube 1.0mLof sulfosalicylic acid solution (1in 10),and mix.Add 2drops of 12Nhydrochloric acid to each tube,and mix.To each tube add 4drops of rhodamine Bsolution (50mg of rhodamine Bdiluted with hydrochloric acid to 100.0mL),and mix.Add 1.0mLof diisopropyl ether.Screw the caps on tightly,shake the tubes by hand for 1minute,accurately timed,releasing any pressure build-up by loosening the caps slightly.Recap the tubes and allow the phases to separate.Transfer 0.5mLof the diisopropyl ether layer from each tube to clean tubes.Visually compare the ether layers:the color of the ether layer from the Injection is not darker than that from the Standard thallium solution.
Iron— Into separate cavities of a spot plate,place 0.1mLof the Injection and 0.1mLof Standard Iron Solution(see Iron á241ñ)diluted with water to a concentration of 5µg per mL.Add to each cavity 0.1mLof hydroxylamine hydrochloride solution (1in 10),1mLof sodium acetate solution (1in 4),and 0.1mLof 0.5%dipyridyl solution (0.5g of 2,2¢-dipyridyl dissolved in 100mLof water containing 0.15mLof hydrochloric acid),and mix.After 5minutes,the color of the specimen of Injection is not darker than that of the Standard Iron Solution.
Copper—
Standard copper solution— Dissolve 0.982g of CuSO4·5H2Oin 1000mLof 0.1Nhydrochloric acid.Transfer 2.0mLof this solution to a 100-mLvolumetric flask,dilute with 0.1Nhydrochloric acid to volume,and mix to obtain a Standard solution containing 5µg of copper per mL.
Procedure— Into separate cavities of a spot plate,place 0.2mLof the Injection and 0.2mLof Standard copper solution.Add to each cavity 0.2mLof water and 0.1mLof iron thiocyanate solution (1.5g ferric chloride and 2g potassium thiocyanate dissolved in water and diluted with water to 100.0mL).Mix,then add 0.1mLof sodium thiosulfate solution (1in 100),and again mix.The time required for the specimen of Thallous Chloride Tl 201Injection to decolorize is equal to or longer than that observed for the Standard copper solution.
Other requirements— It meets the requirements under Injections á1ñ,except that the Injection may be distributed or dispensed prior to the completion of the test for Sterility,the latter test being started on the day of final manufacture,and except that it is not subject to the recommendations 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 mLof Injection by 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 1895
Phone Number:1-301-816-8305