Ganciclovir for 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

Ganciclovir for Injection is a freeze-dried powder prepared by the neutralization of Ganciclovir with the aid of Sodium Hydroxide. It contains NLT 90.0% and NMT 110.0% of the labeled amount of ganciclovir (C₉H₁₃N₅O₄), calculated on the anhydrous basis.

[CAUTION-Handle Ganciclovir for Injection with great care because it is a potent cytotoxic agent and suspected carcinogen.]

2 IDENTIFICATION

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

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B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-Aug-2024)

3 ASSAY

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3.1 PROCEDURE

Mobile phase: Dissolve 1.4 g of monobasic ammonium phosphate in 500 mL of water. Add 1.2 mL of 85% phosphoric acid and dilute with water to 1000 mL. (USP 1-Aug-2024)

Internal standard solution: 0.15 mg/mL of hypoxanthine in water

Standard stock solution: 0.25 mg/mL of USP Ganciclovir RS in water

Standard solution: 0.05 mg/mL of USP Ganciclovir RS prepared as follows. Transfer a suitable volume of the Standard stock solution, add 10% of the ask volume of the Internal standard solution, and dilute with Mobile phase to volume.

Sample stock solution: Nominally 1 mg/mL of ganciclovir, from Ganciclovir for Injection in water

Sample solution: Nominally 0.05 mg/mL of ganciclovir prepared as follows. Transfer a suitable volume of the Sample stock solution, add 10% of the ask volume of the Internal standard solution, and dilute with Mobile phase to volume.

3.2 Chromatographic system

Mode: LC

Flow rate: 1.2 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: Standard solution

[NOTE-The relative retention times for hypoxanthine and ganciclovir are about 0.55 (USP 1-Aug-2024) and 1.0, respectively.]

Suitability requirements

(USP 1-Aug-2024)

Tailing factor: NMT 2.0 for ganciclovir (USP 1-Aug-2024)

Relative standard deviation: NMT 2.0% for the peak response ratio of ganciclovir to hypoxanthine (USP 1-Aug-2024)

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ganciclovir (C₉H₁₃N₅O₄) in the portion of Ganciclovir for Injection taken:

Result = (R_U/R_S) x (C_S/C_U) x 100

R_U = peak response ratio of ganciclovir to the internal standard from the Sample solution

R_S = peak response ratio of ganciclovir to the internal standard from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0% on the anhydrous basis

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4 IMPURITIES

4.1 ORGANIC IMPURITIES

Mobile phase, Internal standard solution, Standard stock solution, Standard solution, Sample stock solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Guanine stock solution: 0.05 mg/mL of USP Guanine RS prepared as follows. Weigh and transfer a suitable quantity of USP Guanine RS to a suitable volumetric flask. Add water to 50% of the flask volume and 1.5% of the flask volume of hydrochloric acid, and sonicate to dissolve. Dilute with water to volume.

Guanine solution: 0.005 mg/mL of USP Guanine RS in Mobile phase from Guanine stock solution

Sensitivity solution: 0.05 µg/mL each of USP Ganciclovir RS and USP Guanine RS in Mobile phase, prepared from the Standard stock solution and Guanine solution

4.2 System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

Relative standard deviation: NMT 2.0% for the peak response ratio of ganciclovir to hypoxanthine, Standard solution

Tailing factor: NMT 2.0 for ganciclovir, Standard solution

Signal-to-noise ratio: NLT 10 for each guanine and ganciclovir, Sensitivity solution

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Ganciclovir for Injection taken:

Result = (R_U/R_S) x (C_S/C_U) x (1/F) x 100

R_U = peak response ratio of each degradation product to the internal standard from the Sample solution

R_S = peak response ratio of ganciclovir to the internal standard from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.1%.

Table 1

5 SPECIFIC TESTS

5.1 PH (791)

Sample: Constituted as directed in the labeling.

Acceptance criteria: 10.8-11.4

5.2 WATER DETERMINATION (921), Method I

Analysis: Proceed as directed in the chapter, except for the following modifications. Use a mixture of anhydrous formamide and methanol (1:1) instead of methanol as the titration vessel solvent. The reagent volume required to condition the titration vessel solvent is NMT 10% of the initial volume of solvent. The concentration of Ganciclovir for Injection in the titration vessel is NMT 7 mg/mL.

Acceptance criteria: NMT 3.0%

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5.3 BACTERIAL ENDOTOXINS TEST (85)

Meets the requirements (USP 1-Aug-2024)

5.4 PARTICULATE MATTER IN INJECTIONS (788)

Meets the requirements for small-volume injections

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5.5 STERILITY TESTS (71)

Meets the requirements

(USP 1-Aug-2024)

5.6 INJECTIONS AND IMPLANTED DRUG PRODUCTS (1)

At the time of use, it meets the requirements for Constituted Solutions.

6 ADDITIONAL REQUIREMENTS

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6.1 PACKAGING AND STORAGE

Preserve in tightly closed containers. Store at controlled room temperature. (USP 1-Aug-2024)

6.2 LABELING

Label it to state that it is to be handled with great care because it is a potent cytotoxic agent and suspected carcinogen.

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6.3 USP REFERENCE STANDARDS (11)

USP Ganciclovir RS

USP Guanine RS

2-Amino-1,7-dihydro-6H-purin-6-one.

C₅H₅N₅O 151.13 (USP 1-Aug-2024)