Ioversol

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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C₁₈H₂₄I₃N₃O₉  807.12 (IRA 1-May-2021)

1,3-Benzenedicarboxamide, N,N'-bis(2,3-dihydroxypropyl)-5-[(hydroxyacetyl) (2-hydroxyethyl)amino]-2,4,6-triiodo-;

N,N'-Bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl) glycolamido]-2,4,6-triiodoisophthalamide CAS RN^®: 87771-40-2; UNII: N3RIB7X24K.

1 DEFINITION

loversol contains NLT 97.0% and NMT 101.0% of ioversol (C₁₈H₂₄I₃N₃O₉), calculated on the anhydrous basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

B.

Sample: About 500 mg

Analysis: Heat the Sample in a crucible.

Acceptance criteria: Violet vapors are evolved.

3 ASSAY

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3.1 PROCEDURE

Sample solution:

Transfer about 500 mg of loversol to a glass-stoppered 125-mL conical flask, add 12 mL of 5 N sodium hydroxide, 20 mL of water, and 1 g of powdered zinc. Connect the conical flask to a reflux condenser, and reflux for 30 min. Cool the flask to room temperature, rinse the condenser with 20 mL of water, disconnect the flask from the condenser, and filter the mixture. Rinse the flask and filter thoroughly, adding the rinsings to the filtrate. Add 40 mL of 2 N sulfuric acid, and titrate immediately.

Titrimetric system

Mode: Direct titration

Titrant: 0.05 N silver nitrate VS

Endpoint detection: Potentiometric

Electrode system: Silver-silver chloride double junction reference electrode and silver billet electrode

Analysis

Sample: Sample solution

Titrate with the Titrant determining the endpoint potentiometrically. Each milliliter of 0.05 N silver nitrate is equivalent to 13.45 mg of ioversol (C₁₈H₂₄I₃N₃O₉).

Acceptance criteria: 97.0%-101.0% on the anhydrous basis (IRA 1-May-2021)

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

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4.2 IODINE AND IODIDE

Standard solution: Transfer 2 mL of 0.25 mg/mL of potassium iodide in water to a 50-mL glass-stoppered cylinder, and add 13 mL of water.

Sample solution: Dissolve 2.0 g of loversol in water in a 50-mL glass-stoppered cylinder, and dilute with water to 15 mL..

Analysis: To the 50-mL glass-stoppered cylinders with the Standard solution and Sample solution, add 5 mL each of diluted sulfuric acid and toluene. Shake vigorously, and allow the layers to separate. The toluene layer shows no red color. Add 1 mL of 20 mg/mL of sodium nitrite solution to both the Standard solution and Sample solution, and shake.

Acceptance criteria: Any red color in the toluene layer of the Sample solution is not darker than that of the Standard solution (NMT (IRA 1-May-2021) 0.02% of iodide).

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4.3 ORGANIC IMPURITIES

Mobile phase: Acetonitrile and water (0.5: 99.5)

Standard solution: 1.0 µg/mL of USP lohexol Related Compound B RSA (IRA 1-May-2021) and 5.0 µg/mL of USP loversol Related Compound B RS in water

Sample solution: 1000 µg/mL of loversol in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; packing L7

Temperature: 35 ± 0.5°

(IRA 1-May-2021)

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

[NOTE-See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between iohexol related compound B (IRA 1-May-2021) and ioversol related compound B

Relative standard deviation: NMT 5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each (IRA 1-May-2021) related compound in the portion of loversol taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each related compound from the Sample solution

r_S = average peak response of each corresponding related compound from the Standard solution s

C_S = concentration of USP lohexol Related Compound B RS Standard solution (µg/mL) 2A (IRA 1-May-2021) or USP loversol Related Compound B RS in the Standard solution (μg/mL)

C_U = concentration of loversol in the Sample solution (µg/mL)

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method 1: NMT 5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. Store at 25°, excursions permitted between 15° and 30°.

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USP REFERENCE STANDARDS (11)

USP lohexol Related Compound B RS

5-Amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide.

C₁₄H₁₈I₃N₃O₆  705.03 (IRA 1-May-2021)

USP loversol RS

(IRA 1-May-2021)

USP loversol Related Compound B RS

N,N'-Bis(2,3-dihydroxypropyl)-5-[{(N-(2-hydroxyethyl)amino)-2-oxoethoxy]-2,4,6-triiodoisophthalamide; also known as N,N'-Bis(2,3-dihydroxypropyl)-5-[(N-(2-hydroxyethyl)-carbamoyl)methoxy]-2,4,6-triiodoisophthalamide.

C₁₈H₂₄I₃N₃O₉  807.12 (IRA 1-May-2021)