Technetium Tc 99m Mertiatide 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 Mertiatide Injection is a sterile, aqueous solution, suitable for intravenous injection, that contains radioactive technetium (^99mTc) in the form of a chelate of mertiatide. It contains NLT 90.0% and NMT 110.0% of the labeled amount of ^99mTc as mertiatide complex expressed in megabecquerels (millicuries or microcuries) per milliliter at the date and time indicated in the labeling. It contains uncomplexed betiatide, a suitable ^99mTc reducing agent, a transfer ligand, and stabilizers.

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: After completing the Analysis for Procedure 2 (Simultaneous determination of free pertechnetate and ^99mTc mertiatide) in the Radiochemical Purity test, examine the radiochromatograms obtained.

Acceptance criteria: The chromatogram shows the retention time of the major peak obtained with the Sample solution is between 10 and 14 min. (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 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 the 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 (Determination of hydrolyzed reduced technetium)

Chromatographic system

(See Chromatography 〈621〉, General Procedures, Paper Chromatography.)

Mode: Paper chromatography

Adsorbent: 25-mm × 20-cm strip of chromatographic paper

Application volume: About 5–10 μL (100–250 μCi)

Developing solvent system: Acetonitrile and water (60:40)

Analysis: Place the Injection 15 mm from the bottom of the Adsorbent. Immediately develop the chromatogram by ascending chromatography using the Developing solvent system until the solvent front has moved about 13 cm from the origin. Remove the strip, and allow to dry. Determine the radioactivity distribution by scanning the chromatogram using a suitable collimated radiation detector.

Calculate the percentage of hydrolyzed reduced technetium:

Result = (A_ht/B_S) × 100

A_ht = sum of all the peaks at or near the origin, where R is less than 0.25

B_S = sum of all of the peaks

Acceptance criteria: NMT 2.0%

Procedure 2 (Simultaneous determination of free pertechnetate and 99mTc mertiatide)

Solution A: 1.36 g/L of monobasic potassium phosphate in water. To each liter of this solution add 1.0 mL of triethylamine, and adjust with 1.0 N hydrochloric acid to a pH between 4.9 and 5.1.

Solution B: 1.36 g/L of monobasic potassium phosphate prepared as follows. Transfer a suitable amount of monobasic potassium phosphate to 900 mL of water, and add 100 mL of tetrahydrofuran to obtain a solution containing 1.36 g per L. To each liter of this solution, add 1.0 mL of triethylamine, and adjust with 1.0 N hydrochloric acid to a pH between 4.9 and 5.1.

Mobile phase: See Table 3. Before injection, equilibrate the system for 15 min with a Mobile phase consisting of a mixture of 90% Solution A and 10% Solution B.

Table 3

Sample solution: Immediately before testing, dilute a portion of the Injection with Water for Injection to obtain a concentration between 400 and 600 μCi. [Note—The extent to which the sample is diluted is determined by the sensitivity of the radiometric detector.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Gamma-ray detector

Column: 3.9-mm × 15-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

Analysis

[Note—The retention times for ^99mTc pertechnetate and ^99mTc mertiatide are 1.8–2.2 min and 10–14 min respectively.]

Calculate the percentage of ^99mTc pertechnetate:

Result = (r_pt/r_S) × 100

r_pt = peak response of 99mTc pertechnetate

r_S = sum of all peak responses

Calculate the percentage of 99mTc mertiatide:

Result = (r_mt/r_S') × 100

r_mt = peak response of 99mTc mertiatide

r_S′ = sum of all peak responses

Acceptance criteria

^99mTc pertechnetate: NMT 6.0%

^99mTc mertiatide: NLT 90.0%

5 SPECIFIC TESTS

Add the following:

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

Delete the following:

Other Requirements (USP 1-Dec-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 calibration; the amount of 99mTc as labeled mertiatide 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.