Foscarnet Sodium

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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CNa₃O₅P · 6H₂O 300.04

Phosphinecarboxylic acid, dihydroxy-, oxide, trisodium salt, hexahydrate;

Phosphonoformic acid, trisodium salt, hexahydrate CAS RN®: 34156-56-4.

1 DEFINITION

Foscarnet Sodium contains NLT 98.5% and NMT 101.0% of foscarnet sodium (CNa₃O₅P), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. Identification Tests—General, Sodium〈191〉: Meets the requirements

3 ASSAY

Procedure

Sample solution: 0.2 g of Foscarnet Sodium in 50 mL of water

Titrimetric system

Mode: Direct titration

Titrant: 0.05 M sulfuric acid

Endpoint detection: Potentiometric

Analysis: Titrate the Sample solution with Titrant, determining the endpoint at the first in ection point. Each mL of 0.05 M sulfuric acid is equivalent to 19.20 mg of foscarnet sodium (CNa₃O₅P).

Acceptance criteria: 98.5%–101.0% on the dried basis

4 IMPURITIES

4.1 Limit of Phosphate and Phosphite

Mobile phase: Dissolve 0.1 g of monobasic potassium phthalate in water. Add 2.5 mL of 1 M nitric acid, and dilute with water to 1000 mL.

Standard stock solution 1: 0.28 mg/mL of sodium dihydrogen phosphate monohydrate in water

Standard stock solution 2: 0.43 mg/mL of sodium phosphite pentahydrate in water

Standard solution: Transfer 1 mL each of Standard stock solution 1 and Standard stock solution 2 to a 25-mL volumetric flask, and dilute with water to volume.

Sample solution: 2.4 mg/mL of Foscarnet Sodium in water

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6-mm × 5-cm; packing L23

Flow rate: 1.4 mL/min

Injection volume: 20 μL

4.1.2 System suitability

Sample: Standard solution

4.1.3 Suitability requirements

Resolution: NLT 2.0 between phosphate and phosphite

4.1.4 Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The peak area of phosphate and phosphite from the Sample solution is NMT the area of the corresponding peak of the Standard solution (0.3% of phosphate and 0.3% of phosphite).

4.2 Limit of Foscarnet Related Compound B, Unknown Impurities, and Total Impurities

Solution A: Dissolve 3.2 g of sodium sulfate decahydrate in water. Add 3 mL of glacial acetic acid and 6 mL of 0.1 M sodium pyrophosphate, and dilute with water to 1000 mL.

Solution B: Dissolve 3.2 g of sodium sulfate decahydrate in water. Add 6.8 g of sodium acetate and 6 mL of 0.1 M sodium pyrophosphate, and dilute with water to 1000 mL.

Mobile phase: Solution A and Solution B (70:30). [Note - The pH of this mixture is about 4.4.] To 1000 mL of this solution add 0.25 g of tetrahexylammonium hydrogen sulfate and 100 mL of methanol.

Sample solution: 2.5 mg/mL of Foscarnet Sodium in Mobile phase

System suitability solution: Transfer 2.0 mL of the Sample solution into a 50-mL volumetric flask. Add 5.0 mg of USP Foscarnet Related Compound B RS, and dilute with Mobile phase to volume.

Standard solution: 5.0 μg/mL of Foscarnet Sodium from the Sample solution in Mobile phase

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 10-cm; 3-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: 2.5 times the retention time of foscarnet

4.2.2 System suitability

Sample: System suitability solution

4.2.3 Suitability requirements

Resolution: NLT 7 between foscarnet and foscarnet related compound B

4.2.4 Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The peak area of any individual impurity from the Sample solution is NMT the area of the major peak of the Standard solution (0.2%); the sum of all the peak areas, apart from the major peak, of the Sample solution is NMT twice the area of the major peak of the Standard solution (0.4%). Disregard any peak with a relative retention time less than 0.6 and any peak with an area less than 0.2 times that of the peak of the Standard solution.

4.3 Limit of Foscarnet Related Compound D

Standard solution: 25 μg/mL of USP Foscarnet Related Compound D RS in alcohol

Sample solution: Dissolve 250 mg of Foscarnet Sodium in 9 mL of 0.1 M acetic acid, and add 1 mL of alcohol.

4.3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.31-mm × 25-m; 0.5-μm coating of phase G27

4.3.2 Temperatures

Injector: 200°

Detector: 250°

Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 1 mL/min

Injection volume: 3 μL

Injection type: Split (1:20)

4.3.3 Analysis

Samples: Standard solution and Sample solution

4.3.4 Acceptance criteria

Individual impurities: The peak area of foscarnet related compound D from the Sample solution is NMT the peak area of the Standard solution (0.1%).

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 20 mg/mL of Foscarnet Sodium in a carbon dioxide-free aqueous solution

Acceptance criteria: 9.0–11.0

Loss on Drying 〈731〉

Sample: 0.1 g

Analysis: Dry the Sample at 150° for at least 15 min.

Acceptance criteria: 35.0%–37.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store at room temperature.

USP Reference Standards 〈11〉

USP Foscarnet Related Compound B RS

Disodium (ethoxyoxidophosphanyl)formate.

C₃H₅Na₂O₅P 198.02

USP Foscarnet Related Compound D RS

O,O-Diethyl ethoxycarbonylphosphonate.

C₇H₁₅O₅P 210.16

USP Foscarnet Sodium RS