Cidofovir 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

Cidofovir Injection is a sterile aqueous solution. It contains an amount of cidofovir equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of anhydrous cidofovir (C₈H₁₄N₃O₆P).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970

Standard solution: 7.5 µg/mL of USP Cidofovir RS in water. Adjust with 0.1 N sodium hydroxide to a pH of 7.5.

Sample solution: Nominally 7.5 µg/mL of cidofovir from Injection in water

Acceptance criteria: Meets the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Solution A: Acetonitrile and water (40:60)

Buffer: Dissolve 1.2 g of dibasic ammonium phosphate and 2.0 g of tetrabutylammonium phosphate in 1 L of water. Adjust with ammonium hydroxide to a pH of 9.2.

Mobile phase: Solution A and Buffer (20:80)

Standard solution: 0.17 mg/mL of USP Cidofovir RS in water. [NOTE-0.17 mg/mL of USP Cidofovir RS is equivalent to 0.15 mg/mL of cidofovir on the anhydrous basis.]

Sample solution: Nominally 0.15 mg/mL of cidofovir from Injection in water

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 274 nm

Column: 4.6-mm x 25-cm; 5-µm packing 11

Temperatures

Autosampler: 10"

Column: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of anhydrous cidofovir (C₈H₁₄N₃O₆P) in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of cidofovir from the Sample solution

r_S = peak response of cidofovir from the Standard solution

C_S = concentration of USP Cidofovir RS in the Standard solution (mg/mL)

C_U = nominal concentration of anhydrous cidofovir in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0% on the anhydrous basis

4 IMPURITIES

Organic Impurities

Mobile phase and Chromatographic system: Proceed as directed in the Assay with a run time NLT 4.5 times the retention time of cidofovir.

Standard solution: 0.0015 mg/mL of USP Cidofovir RS in water

Sample solution: Nominally 1.5 mg/mL of anhydrous cidofovir from Injection in water

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) x (C_S/C_U) × (1/F) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of cidofovir from the Standard solution

C_S = concentration of USP Cidofovir RS in the Standard solution (mg/mL)

C_U = nominal concentration of anhydrous cidofovir in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a 1-[(S)-2,3-Dihydroxypropyl]cytosine.

^b These are included in the table for identification only. These are process impurities controlled in the drug substance. They are not to be included in the total impurities.

^c 1-[(S)-3-Hydroxy-2-(phosphonomethoxy)propyl]uracil.

^d 1-[(S)-3-Bromo-2-(phosphonomethoxy)propyl]cytosine.

5 SPECIFIC TESTS

pH 〈791〉: 7.1–7.7

Particulate Matter in Injections 〈788〉: Meets the requirements

Bacterial Endotoxins Test 〈85〉: NMT 1 USP Endotoxin Unit/mg of anhydrous cidofovir

Sterility Tests 〈71〉: Meets the requirements

Change to read:

Osmolality and Osmolarity 〈785〉

Osmolarity: (Official 1-Aug-2022) 550–650 mOsmol/L

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Cidofovir RS

USP Endotoxin RS