Technetium Tc 99m Mebrofenin Injection
»Technetium Tc 99m Mebrofenin Injection is a sterile aqueous solution of Stannous Fluoride and Mebrofenin labeled with radioactive technetium Tc 99m suitable for intravenous administration.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of 99mTc,as the complex with mebrofenin,expressed in megabecquerels (or in millicuries)per mLat the time indicated in the labeling.It may contain antimicrobial agents and buffers.Other chemical forms of radioactivity do not exceed 10.0percent of the total radioactivity.
Packaging and storage— Preserve in single-dose or in multiple-dose containers,at controlled room temperature.
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 99mTc as labeled mebrofenin expressed as total megabecquerels (or millicuries)and the concentration as megabecquerels per mL(or as millicuries per mL)on the date and 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 99mTc is 6.0hours.
pHá791ñ: between 4.2and 5.7.
Radiochemical purity— [NOTE—The determination of radiochemical purity for this product requires the use of two separate chromatographic methods.]
Method 1—
pH 6.8PHOSPHATE BUFFER—Mix 64mLof 0.2Mmonobasic sodium phosphate and 61mLof 0.1Mdibasic sodium phosphate in a 1-liter volumetric flask,dilute with water to volume,and mix.
MOBILE PHASE —Prepare a filtered and degassed mixture of methanol and pH6.8phosphate buffer(625:375).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
CHROMATOGRAPHIC SYSTEM (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 3.9-mm ×30-cm column that contains 10-µm packing L1.It is also equipped with a flow-through gamma ray detector having a cell volume of about 10µL.Aconstant flow rate of about 1mLper minute is maintained,and counts are recorded and charted at about 5-second intervals.
PROCEDURE —Constitute the Injection,and allow to stand for 15minutes.Chromatograph a volume of Injection,with activity of 0.6to 15MBq (16to 400µCi),and record the chromatogram.The resolution between the secondary characteristic peak,eluting at about 3.5minutes,and the principal peak,eluting at about 6minutes,is not less than 1.5.The time interval between the elution of the Tc 99m pertechnetate peak,at about 2minutes,and the principal peak is not less than 3.0minutes.If the foregoing criteria are met,record the counts for the pertechnetate Tc 99m peak,the two complex peaks,a representative baseline segment,and the total counts for the chromatogram.Calculate the percentage of complexed radioactivity in the two characteristic peaks taken by the formula:
100C/(T-P),
in which Cis the count of the complex peak of interest,Tis the total count,and Pis the pertechnetate peak count,each being corrected for the corresponding baseline count.The complexed radioactivity is not less than 90.0%in the principal peak and between 1%and 6%in the second characteristic peak.Calculate the percentage of all other complexed radioactivity (this excludes the main,secondary,and free pertechnetate peaks)taken by the formula:
100K/(T-P),
in which Kis the sum of all other peaks,and Tand Pare as defined above.Record the result for use in the calculation as directed under Method 2.
Method 2—
CHROMATOGRAPHIC SYSTEM A (see Chromatography á621ñ)—Prepare a 1.0-×12.5-cm silicic acid-impregnated glass microfiber strip by dipping it in a 10%sodium chloride solution and removing the excess liquid by blotting.Dry the strip by heating in an oven at about 80.Apply about 5µLof the Injection with activity of about 3.7MBq (100µCi)about 1.5cm from one end of the strip,and immediately develop the chromatogram in a chromatographic chamber containing saturated sodium chloride solution until the solvent front reaches a level about 1cm from the top of the strip.Remove the strip from the chamber,and allow to air-dry.Separate the top and bottom portions of the chromatogram by cutting the strip in half,and record the counts separately for each portion.Calculate the percentage of unreduced pertechnetate taken by the formula:
100P/(P+C),
in which Pis the count from the top half of the strip,and Cis the count from the bottom half of the strip.
CHROMATOGRAPHIC SYSTEM B —Proceed as directed under Chromatographic system Aexcept to use a 1.0-×12.5-cm silica gel-impregnated glass microfiber strip,without preliminary treatment,and a mixture of acetonitrile and water (3:1)as the developing solvent.Calculate the percentage of reduced hydrolyzed Tc 99m taken by the formula:
100R/(R+D),
in which Ris the count from the bottom half of the strip,and Dis the count from the top half of the strip.The sum of the percentage of unreduced pertechnetate from System A,the percentage of reduced hydrolyzed Tc 99m from System B,and the percentage of other complexed radioactivity determined from Method 1is not greater than 10.0%.
Biological distribution— Inject 0.25mLof Injection containing between 15and 19MBq (0.4and 0.5mCi)into the external jugular vein of each of three anesthetized male rats weighing between 150and 350g,and from which food has been withheld for 15to 24hours prior to the test.Thirty minutes after the injection,sacrifice the animals and carefully remove the liver,kidneys,and gastrointestinal tract of each rat.Place the organs in separate counting containers.Using a suitable counting assembly,determine the radioactivity in each container.Correct radioactivity measurements for decay.Determine the percentages of radioactivity in the liver,kidneys,and gastrointestinal tract taken by the formula:
100(A/B),
in which Ais the radioactivity,in counts per minute,in the organ,and Bis the average injected radioactivity,in counts per minute,in the corresponding standards.Not less than 75%of the injected radioactivity is found in the gastrointestinal tract,not more than 10%in the liver,and not more than 5%in the kidneys in not less than 2of the rats.
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 for Injections á1ñ,except that it may be distributed and dispensed prior to the completion of the test for Sterility,the latter being started on the day of manufacture,and except that it is not subject to the recommendation on Volume in Container.
Assay for radioactivity 821— Using a suitable counting assembly (see Selection of a Counting Assembly),determine the radioactivity,in MBq (or in mCi)per mL,of 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 1857
Phone Number:1-301-816-8305