Technetium Tc 99m Bicisate 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 Bicisate Injection is a sterile, clear, colorless solution, suitable for intravenous administration, of bicisate dihydrochloride complexed to radioactive technetium (^99mTc). It contains NLT 90.0% and NMT 110.0% of the labeled amount of ^99mTc as a complex with bicisate, 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.

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 factors of the spots for Tc 99m bicisate and/or Tc(IV) 99m bicisate in the chromatogram of the Sample correspond with the ranges stated in the test for Radiochemical Impurities. (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 (or millicuries) 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 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.

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Radiochemical Purity

Sample solution: Prepare four vials of Injection and perform the test on each vial.

Chromatographic system

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

Mode: TLC

Adsorbent: 2.5-cm × 7.5-cm chromatographic silica gel sheet

Application volume: About 5 μL

Developing solvent system: Ethyl acetate

Analysis

Sample: The Sample solution used to perform this test is also used to perform the test for Radiochemical Impurities. Perform the tests in parallel with a minimal delay in spotting of the chromatographic media following the 30-min Injection incubation period. (USP 1-Dec-2024)

Place the Sample solution about 2 cm from the bottom of the Adsorbent and allow to dry for 5–10 min. Position the plate in a pre-equilibrated chromatographic chamber containing the Developing solvent system, and develop the chromatogram until the solvent front has moved 5 cm from the origin. Remove the plate from the chamber, and allow to dry. Cut the chromatographic sheet 4.5 cm from the bottom. Separately count the activity on each piece in a dose calibrator or a gamma counter. The activity on the upper portion contains the 99mTc bicisate complex, and the activity on the lower section contains all radioimpurities.

Calculate the percentage of radiochemical purity of the Injection taken:

Result = 100P/(P + C)

P = count from the top part of the sheet

C = count from the bottom part of the sheet

Acceptance criteria: NLT 90% of the total radioactivity is found as Tc99m bicisate. Calculate the mean percentage of radiochemical purity of the four test vials.

5 IMPURITIES

Change to read:

Radiochemical Impurities

(USP 1-Dec-2024)

Chromatographic system

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

Mode: TLC

Adsorbent: 2.5-cm × 7.5-cm reverse-phase thin-layer chromatographic plate (or equivalent)

Developing solvent system: Acetone and 0.5 M ammonium acetate (60:40)

Application volume: About 2 μL

Analysis

Sample: Sample solution used to perform the test for Radiochemical Purity. Perform the tests in parallel with a minimal delay in spotting of the chromatographic media following the 30-min Injection incubation period.

Apply the Sample 1 cm from the bottom of the Adsorbent, and allow the spot to air-dry thoroughly. Develop the chromatogram until the solvent front has moved 7 cm from the origin. Remove the plate from the chamber and air-dry. Using a suitable calibrated scanner, determine the compounds present by calculating the retention factors for all peaks present. Compounds and approximate R values are shown in Table 3.

Table 3

Calculate the quantity of ^99mTc(IV) ligand in the Injection by subtracting the ^99mTc bicisate percentage obtained in the test for Radiochemical Purity from the combined ^99mTc bicisate and ^99mTc(IV) bicisate area percentage obtained in the test for Radiochemical Impurities.

Acceptance criteria: The sum of the impurities is NMT 10%.

6 SPECIFIC TESTS

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

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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)

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, at controlled room temperature.

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 bicisate expressed as total megabecquerels (or millicuries) per milliliter at the time of calibration; 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.