Technetium Tc 99m Tetrofosmin 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 Tetrofosmin Injection is a sterile, aqueous solution, suitable for intravenous injection, that contains ^99mTc in the form of a complex of tetrofosmin. It contains NLT 90.0% and NMT 110.0% of the labeled amount of ^99mTc as tetrofosmin complex expressed in megabecquerels (or millicuries) per milliliter at the date and time indicated in the labeling. Other chemical forms of radioactivity are NMT 10.0% of the total radioactivity. It may contain reducing agents, stabilizers, and buffers. It contains no antimicrobial agents.

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.

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B. Radiochemical Identity

Acceptance criteria: The retardation factor of the spot for Tc 99m tetrofosmin in the chromatogram of the Injection corresponds with that stated in the test for Radiochemical Purity. (USP 1-Dec-2024)

3 ASSAY

Radioactive Concentration (Strength)

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

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

Acceptance criteria: 90.0%–110.0% of the labeled amount of ^99mTc at the date and 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

Chromatographic system

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

Mode: TLC

Adsorbent: 2-cm × 20-cm instant thin-layer chromatographic silica gel strip

Application volume: 10–20 μL

Developing solvent system: Acetone and dichloromethane (35:65)

Analysis: Apply the Injection about 3.0 cm from the bottom of the Adsorbent. Immediately develop the chromatogram in the Developing solvent system by ascending chromatography to a height of 15 cm and allow to air-dry. Determine the radioactivity distribution of the chromatogram by scanning with a suitable radiation detector. The R_F value of the ^99mTc tetrofosmin spot is approximately 0.5.

Acceptance criteria: The sum of radioactivity at the solvent front (unbound pertechnetate) and the origin (reduced hydrolyzed technetium and hydrophilic impurities) is NMT 10%.

5 SPECIFIC TESTS

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

pH 〈791〉: 8.3–9.1

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-Dec-2024)

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

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Other Requirements (USP 1-Dec-2024)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store in adequately shielded, single-dose or multiple-dose containers. Protect from light. Store at a temperature not exceeding 25°.

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 calibration; the amount of ^99mTc as labeled tetrofosmin expressed as total megabecquerels (or millicuries) and the concentration as megabecquerels per milliliter (or as millicuries per milliliter) 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 6.0 h.