Tetraxetan

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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C₁₆H₂₈N₄O₈ 404.42

1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid;

2,2′,2′′,2′′′-(1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetryl)tetraacetic acid. CAS RN®: 60239-18-1.

1 DEFINITION

Tetraxetan contains NLT 98.5% and NMT 101.5% of tetraxetan (C₁₆H₂₈N₄O₈), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K

B. The retention time of the tetraxetan peak of the Sample solution corresponds to that of the Standard solution, as obtained in the test for Organic Impurities.

3 ASSAY

Procedure

Sample solution: Dissolve 150 mg of Tetraxetan in 15 mL of water and add 30 mL of methanol.

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N sodium hydroxide VS

Endpoint detection: Potentiometric

Analysis

Sample: Sample solution

Titrate with Titrant using a glass electrode and a silver–silver chloride electrode system. Perform a blank determination and make any

necessary correction.

Calculate the percentage of tetraxetan (C₁₆H₂₈N₄O₈) in the portion of Tetraxetan taken:

Result = [(V − B) × N × F/W] × 100

V = volume of Titrant consumed by the Sample solution to reach the first endpoint (mL)

B = blank Titrant volume (mL)

N = normality of the Titrant (mEq/mL)

F = equivalency factor for tetraxetan, 202.2 mg/mEq

W = weight of the sample taken (mg)

Acceptance criteria: 98.5%–101.5% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Buffer: 0.6 g/L of monobasic sodium phosphate in water. Adjust with phosphoric acid to a pH of 2.1.

Solution A: Acetonitrile and water (50:50)

Solution B: Buffer

Mobile phase: See Table 1.

Table 1

System suitability solution: 10 mg/mL of USP Tetraxetan RS and 30 μg/mL of USP Tetraxetan Related Compound A RS in water

Sensitivity solution: 5 μg/mL of USP Tetraxetan RS in water

Sample solution: 10 mg/mL of Tetraxetan in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 200 nm

Column: 4.6-mm × 15-cm; 3-μm packing L109

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Sensitivity solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between tetraxetan and tetraxetan related compound A, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of each individual impurity in the portion of Tetraxetan taken:

Result = (r_U /r_T ) × 100

r_U = peak response of each impurity

r_T = sum of all the peak responses

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 15.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Tetraxetan RS

USP Tetraxetan Related Compound A RS

2,2′,2′′-[10-(2-Ethoxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl]triacetic acid.

C₁₈H₃₂N₄O₈ 432.47 (USP 1-May-2021)