Technetium Tc 99m Sestamibi Injection
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 99mTc suitable for intravenous administration. It contains not less than 90 percent and not more than 110 percent of the labeled amount of 99mTc as a complex with sestamibi, expressed in megabecquerels (or in milicuries) per mL at the time indicated in the labeling. It contains reducing agents, a buffer, and an inert filler. Other chemical forms of radioactivity do not exceed 10 percent 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 Labeling under Injections 
1
: the time and date of constitution; the volume of constitution; the amount of 99mTc as labeled sestamibi expressed as total megabecquerels (or millicuries) per mL at 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 6.0 hours.
1: the time and date of constitution; the volume of constitution; the amount of 99mTc as labeled sestamibi expressed as total megabecquerels (or millicuries) per mL at 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 6.0 hours.
Bacterial endotoxins 85—
It contains not more than 175/V USP Endotoxin Units per mL, in which V is the maximum recommended total dose, in mL, at the expiration date or time.
85—
It contains not more than 175/V USP Endotoxin Units per mL, in which V is the maximum recommended total dose, in mL, at the expiration date or time.
pH 791:
between 5.0 and 6.0.
791:
between 5.0 and 6.0.
Radiochemical purity—
Preparation of the test vials—
Constitute each of 4 vials with 1 mL (1875 ± 187.5 MBq, or 50 ± 5 mCi) of Sodium Pertechnetate Tc 99m Injection. Heat the vials in boiling water for 10 minutes. After heating, allow the vials to cool to room temperature for 15 minutes.
Method 1
(Thin-layer chromatography)—Apply 1 to 2 µL of Injection about 1 cm from the bottom of a 25-mm × 7.75-cm reverse-phase chromatographic plate, and allow to dry (see Chromatography 621). Position the plate in a chromatographic chamber and develop the chromatograms in a freshly prepared (not more than 4 hours) 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 6 cm 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. A mean of not less than 90% (area %) of the radioactivity is found at an RF value between 0.3 and 0.6. Free pertechnetate is located at about the RF 0.8 to 1.0, and radiocolloid is located at about RF 0 to 0.1. The sum of the mean percentages of free pertechnetate and colloid does not exceed 10%.
621). Position the plate in a chromatographic chamber and develop the chromatograms in a freshly prepared (not more than 4 hours) 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 6 cm 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. A mean of not less than 90% (area %) of the radioactivity is found at an RF value between 0.3 and 0.6. Free pertechnetate is located at about the RF 0.8 to 1.0, and radiocolloid is located at about RF 0 to 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, 0.05 M ammonium sulfate solution, and acetonitrile (45:35:20). Make adjustments if necessary (see System Suitablity under Chromatography 621).
621).
chromatographic system (see Chromatography 621)—
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 2 mL per minute. If 99mTc pentamibi dimethylvinyl isonitrile is present, the relative retention between the 99mTc sestamibi peak and the 99mTc pentamibi dimethylvinyl isonitrile peak is 1.3 to 1.5.
621)—
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 2 mL per minute. If 99mTc pentamibi dimethylvinyl isonitrile is present, the relative retention between the 99mTc sestamibi peak and the 99mTc pentamibi dimethylvinyl isonitrile peak is 1.3 to 1.5.
procedure—
Inject about 5 µL (9.375 MBq or 250 µCi) of Sodium Pertechnetate Tc 99m Injection into the chromatograph, and adjust the integrator/recording device so that the peak is 25% to 100% of full scale. Separately inject equal volumes (about 5 µL, 9.375 MBq, or 250 µCi) 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 5 to 10 minutes. The retention time for 99mTc pentamibi dimethylvinyl isonitrile is about 6 to 13 minutes. Correct for the presence of colloid, which is not measured by this method, taken by the equation:
Cf = [(100%) 
(Ac)] / 100
in which Cf is the correction factor, and Ac is 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. A mean 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.
(Ac)] / 100
Other requirements—
It meets the requirements of the tests for Radionuclide identification and Radionuclidic purity under Sodium Pertechnetate Tc 99m Injection. It meets also the requirements for Injections 1, 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.
1, 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 the Injection by use of a calibrated system.
821—
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—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Ian DeVeau, Ph.D.
Director, Veterinary Drugs and Radiopharmaceuticals 1-301-816-8178 |
(RMI05) Radiopharmaceuticals and Medical Imaging Agents 05 |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
|
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Senior Scientist 1-301-816-8339 |
(MSA05) Microbiology and Sterility Assurance |
USP32–NF27 Page 3671
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.