Technetium Tc 99m Sestamibi Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Technetium Tc 99m Sestamibi Injection is a sterile, aqueous solution of tetrakis (2-methoxy-isobutyl isonitrile) copper (I) tetrafluoroborate that is labeled with radioactive technetium (^99mTc) suitable for intravenous administration. It contains NLT 90% and NMT 110% of the labeled amount of ^99mTc as a complex with sestamibi, expressed in megabecquerels (or in millicuries) per milliliter at the time indicated in the labeling. Other chemical forms of radioactivity are NMT 10% of the total radioactivity. It contains reducing agents, a buffer, and an inert filler.

2 IDENTIFICATION

A. Radionuclidic Identity

(See Radioactivity 〈821〉, Identification of Radionuclides.)

Acceptance criteria: Its gamma-ray spectrum is identical to that of a specimen of 99mTc that exhibits a major photopeak having an energy of 0.140 MeV.

Add the following:

B. Radiochemical Identity

Analysis: Examine the radiochromatograms obtained in the test for Radiochemical Purity, Procedure 2.

Acceptance criteria: The distribution of the radioactivity contributes to the identification of the preparation. (USP 1-Aug-2024)

3 ASSAY

Radioactive Concentration (Strength)

(See Radioactivity 〈821〉, Assay of Radionuclides.)

Analysis: Using a suitable counting assembly, determine the radioactivity, in megabecquerels (or in millicuries) per milliliter, of the Injection by use of a calibrated system.

Acceptance criteria: 90%–110% of the labeled amount of ^99mTc at the time indicated in the labeling

4 PURITY

Radionuclidic Purity

(See Radioactivity 〈821〉.)

Analysis: Using a suitable counting assembly, determine the radioactivity of each radionuclidic impurity, in kilobecquerels per megabecquerel (microcuries per millicurie) of technetium 99m in the Injection by use of a calibrated system.

Acceptance criteria

For Injection prepared from technetium 99m derived from parent molybdenum 99 formed as a result of neutron bombardment of stable molybdenum: See Table 1.

For Injection prepared from technetium 99m derived from parent molybdenum 99 formed as a result of uranium fission—gamma- and beta-emitting impurities: See Table 2.

Table 1

^a Radioactivity of radionuclidic impurity/radioactivity of Tc 99m per administered dose of Injection at the time of administration.

^b Does not exceed 92 kBq (2.5 μCi) per administered dose of the Injection at the time of administration.

Table 2

^a Radioactivity of radionuclidic impurity/radioactivity of Tc 99m present at the time of administration.

^b Use a counting system appropriate for the detection of particulate radiations.

Radiochemical Purity

Procedure 1

Sample solution: Constitute each of four 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 min. After heating, allow the vials to cool to room temperature for 15 min.

Chromatographic system

(See Chromatography 〈621〉, General Procedures, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 25-mm × 7.75-cm reverse-phase chromatographic plate

Application volume: 1–2 μL of Injection

Developing solvent system: Acetonitrile, methanol, tetrahydrofuran, and 3.85% ammonium acetate (40:30:10:20). [Note—The Developing solvent system should be freshly prepared (NMT 4 h before use).]

Analysis: Apply the Sample solution about 1 cm from the bottom of the Adsorbent, and allow to dry. Position the plate in a chromatographic chamber and develop the chromatograms until the solvent front has moved 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.

Acceptance criteria: A mean of NLT 90% (area %) of the radioactivity is found at an R of 0.3–0.6. Free pertechnetate is located at an R_F of 0.8–1.0, and radio-colloid is located at an R of 0–0.1. The sum of the mean percentages of free pertechnetate and colloid is NMT 10%.

Procedure 2

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Mobile phase: Methanol, 0.05 M ammonium sulfate solution, and acetonitrile (45:35:20)

Detector: Gamma-ray detector

Column: 3.9-mm × 30-cm; 10-μm packing L1

Flow rate: 2 mL/min

Injection volume: About 5 μL (9.375 MBq or 250 μCi)

Retention times: ^99mTc pentamibi dimethylvinyl isonitrile is 6–13 min; ^99mTc sestamibi is 5–10 min

Analysis

[Note—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.]

Inject Sodium Pertechnetate Tc 99m Injection into the chromatograph, and adjust the integrator/recording device so that the peak is 25%–100% of full scale. Separately inject equal volumes of the injection. Record the chromatograms, and measure the area percentage for all of the peaks present.

The retention time for ^99mTc sestamibi is 5–10 min and the retention time for ^99mTc pentamibi dimethylvinyl isonitrile is 6–13 min.

Correct for the presence of colloid, which is not measured by this procedure, as follows:

C_f = [(100%) − (A_C)]/100

C_f = correction factor

A_C = mean area percentage for the colloid obtained from the Radiochemical Purity, Procedure 1 test

Obtain the corrected area percentage by multiplying the correction factor (C_f) by the area percentage of the peaks present in the chromatogram.

Acceptance criteria: A mean of NLT 90% (corrected area percentage) of the total radioactivity is represented by ^99mTc sestamibi, and a mean of NMT 5% (corrected area percentage) of the total radioactivity is present as ^99mTc pentamibi dimethylvinyl isonitrile.

5 SPECIFIC TESTS

Add the following:

Appearance: Clear, colorless solution, free from visible particulates (USP 1-Aug-2024)

pH 〈791〉: 5.0–6.0

Change to read:

Bacterial Endotoxins Test 〈85〉: Meets the requirements. The Injection may be distributed or dispensed prior to completion of the test. (USP 1-Aug-2024)

Add the following:

Sterility Tests 〈71〉: Meets the requirements. The Injection may be distributed or dispensed prior to completion of the test. (USP 1-Aug-2024)

Delete the following:

Other Requirements (USP 1-Aug-2024)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers.

Labeling: Label the Injection to include the following, in addition to the information specified under Labeling 〈7〉, Labels and Labeling for Injectable Products: the time and date of constitution; the volume of constitution; the amount of 99mTc as labeled sestamibi expressed as total begabecquerels (or millicuries) per milliliter 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 h.