Ioversol 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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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click www.uspnf.com/rb-ioversol-inj-20241227.

1 DEFINITION

loversol Injection is a sterile solution of loversol in Water for Injection. It contains NLT 95.0% and NMT 105.0% of the labeled amount of ioversol (C₁₈H₂₄I₃N₃O₉) and iodine (I). It may contain small amounts of suitable buffers and Edetate Calcium Disodium as a stabilizer. loversol Injection intended for intravascular use contains no antimicrobial agents.

2 IDENTIFICATION

A. The IR absorption spectrum of a portion of Injection exhibits maxima only at the same wavelengths, when measured using a zinc sulfide cell with a thickness of 0.01-0.2 mm, as that of a similar preparation of USP loversol RS.

B.

Analysis: Heat about 1 mL of Injection in a crucible.

Acceptance criteria: Violet vapors are evolved.

3 ASSAY

3.1 PROCEDURE

Sample solution: Transfer a volume of Injection, nominally equivalent to 500 mg of ioversol, to a suitable glass-stoppered flask, add 12 mL of 5 N sodium hydroxide, 20 mL of water, and 1 g of powdered zinc. Connect the flask to a reflux condenser, and reflux for 30 min. Cool the flask to room temperature, and 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 2N 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: 95.0%-105.0% of the labeled amount of ioversol

4 IMPURITIES

Change to read:

4.1 ORGANIC IMPURITIES

Mobile phase: Acetonitrile and water (0.5: 99.5)

Standard solution: 1.5 µg/mL of USP lohexol Related Compound B RS and 15 µg/mL of USP loversol Related Compound B RS in water

Sample solution: Nominally 1000 µg/mL of ioversol from Injection diluted with water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Temperature: 35 ± 0.5°

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 and ioversol related compound B

Relative standard deviation: NMT 5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each related compound in the portion of Injection 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

C_S = concentration of USP lohexol Related Compound B RS or USP loversol Related Compound B RS in the Standard solution (µg/mL)

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

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

PH (791): 6.0-7.4

BACTERIAL ENDOTOXINS TEST (85): NMT 1.4 USP Endotoxin Units/mL of Injection

OTHER REQUIREMENTS: It meets the requirements in Injections and Implanted Drug Products (1).

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in single-dose containers, preferably of Type I glass, protected from light.

LABELING: Label containers of Injection intended for intravascular injection to direct the user to discard any unused portion remaining in the container.

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

USP loversol RS

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