Technetium Tc 99m Sestamibi Injection, chemical structure, molecular formula, Reference Standards

Technetium Tc 99m Sestamibi Injection

C36H66N6O699mTc

Technetium(1+)-99mTc,hexakis(1-isocyano-2-methoxy-2-methylpropane)-,(OC-6-11)-.
Hexakis(2-methoxy-2methylpropyl isocyanide)[99mTc]technetium(1+) [109581-73-9].

»Technetium Tc 99m Sestamibi Injection is a sterile,aqueous solution of tetrakis(2–methoxy-isobutyl isonitrile)copper(I)tetrafluoroborate that is labeled with 99mTCsuitable for intravenous administrastion.It contains not less than 90percent and not more than 110percent of the labeled amount of 99mTCas a complex with sestamibi,expressed in megabecquerels (or in milicuries)per mLat the time indicated in the labeling.It contains reducing agents,a buffer,and an inert filler.Other chemical forms of radioactivity do not exceed 10percent of the total radioactivity.

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 constitution;the volume of constitution;the amount of 99mTc as labeled sestamibi expressed as total megabecquerels (or millicuries)per mLat the time of constitution;the expiration date and time;the lot number;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.

USP Reference standardsá11ñ— USP Endotoxin RS.

Bacterial endotoxins á85ñ— It contains not more than 175/VUSP Endotoxin Units per mL,in which Vis the maximum recommended total dose,in mL,at the expiration date or time.

pHá791ñ: between 5.0and 6.0.

Radiochemical purity—

Preparation of the test vials— Constitute each of 4vials with 1mL(1875±187.5MBq,or 50±5mCi)of Sodium Pertechnetate Tc 99m Injection.Heat the vials in boiling water for 10minutes.After heating,allow the vials to cool to room temperature for 15minutes.

Method 1 (Thin-layer chromatography)—Apply 1to 2µLof Injection about 1cm from the bottom of a 25-mm ×7.75-cm reverse-phase chromatographic plate,and allow to dry (see Chromatography á621ñ).Position the plate in a chromatographic chamber and develop the chromatograms in a freshly prepared (not more than 4hours)solvent system consisting of a mixture of acetonitrile,methanol,3.85%ammonium acetate,and tetrahydrofuran (4:3:2:1)until the solvent front has moved about 6cm from the origin.Remove the plate and allow it to air-dry.Determine the radioactivity distribution by scanning the chromatogram with a suitable radiation detector.Amean of not less than 90%(area %)of the radioactivity is found at an RFvalue between 0.3and 0.6.Free pertechnetate is located at about the RF0.8to 1.0,and radiocolloid is located at about RF0to 0.1.The sum of the mean percentages of free pertechnetate and colloid does not exceed 10%.

Method 2 (High-pressure liquid chromatography)—

MOBILE PHASE— Prepare a filtered and degassed mixture of methanol,0.05Mammonium sulfate solution,and acetonitrile (45:35:20).Make adjustments if necessary (see System Suitablityunder 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.The flow rate is about 2mLper minute.If 99mTc pentamibi dimethylvinyl isonitrile is present,the relative retention between the 99mTc sestamibi peak and the 99mTc pentamibi dimethylvinyl isonitrile peak is 1.3to 1.5.

PROCEDURE— Inject about 5µL(9.375MBq or 250µCi)of Sodium Pertechnetate Tc 99m Injectioninto the chromatograph,and adjust the integrator/recording device so that the peak is 25%to 100%of full scale.Separately inject equal volumes (about 5µL,9.375MBq,or 250µCi)of the injection under test into the chromatograph,record the chromatograms,and measure the area percentage for all of the peaks present.The retention time for 99mTc sestamibi is about 5to 10minutes.The retention time for 99mTc pentamibi dimethylvinyl isonitrile is about 6to 13minutes.Correct for the presence of colloid,which is not measured by this method,taken by the equation:

Cf=[(100%)-(Ac)]/100,

in which Cfis the correction factor,and Acis the mean area percentage for the colloid obtained from Method 1.Obtain corrected area percentage by multiplying the correction factor (Cf)by the area percentage of the peaks present in the chromatogram.Amean of not less than 90%(corrected area percentage)of the total radioactivity is represented by 99mTc sestamibi,and a mean of not more than 5%(corrected area percentage)of the total radioactivity is present as 99mTc pentamibi dimethylvinyl isonitrile.

Other requirements— It meets the requirements of the tests for Radionuclide identificationand Radionuclidic purityunder Sodium Pertechnetate Tc 99m Injection.It meets also 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 á821ñ— Using a suitable counting assembly (see Selection of a Counting Assembly),determine the radioactivity,in MBq (or in mCi)per mL,of the 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 1863

Phone Number:1-301-816-8305