Valganciclovir for Oral Solution

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

Valganciclovir for Oral Solution contains an amount of valganciclovir hydrochloride (C₁₄H₂₂N₆O₅ · HCl) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of valganciclovir (C₁₄H₂₂N₆O₅)

2 IDENTIFICATION

A. The retention times of the diastereomeric peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

B. The UV spectra of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: 5.75 g/L of ammonium phosphate dibasic in water. Adjust with phosphoric acid to a pH of 2.8.

Solution B: Methanol

Mobile phase: See Table 1.

Table 1

Diluent: 1 mM hydrochloric acid

Standard solution: 0.3 mg/mL of USP Valganciclovir Hydrochloride RS in Diluent

Sample stock solution: Nominally 30 mg/mL of valganciclovir in water prepared as follows. Add 100 mL of water to each of 5 sample bottles of Valganciclovir for Oral Solution and shake well to dissolve the powder. Quantitatively transfer the solutions to a 1000-mL volumetric flask. Dilute with water to volume.

Sample solution: Nominally 0.3 mg/mL of valganciclovir in Diluent prepared from the Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 3.5-µm packing L1

Autosampler temperature: 5°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for the two valganciclovir diastereomer peaks are 0.86 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between the two valganciclovir diastereomer peaks

Tailing factor: NMT 2.0 for the second valganciclovir diastereomer peak

Relative standard deviation: NMT 2.0% for the total areas of the two valganciclovir diastereomer peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valganciclovir (C₁₄H₂₂N₆O₅) in the portion of Oral Solution taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = sum of the peak responses of the valganciclovir diastereomer peaks from the Sample solution

r_s = sum of the peak responses of the valganciclovir diastereomer peaks from the Standard solution

C_s = concentration of USP Valganciclovir Hydrochloride RS in the Standard solution (mg/mL)

C_u = nominal concentration of valganciclovir in the Sample solution (mg/mL)

M_r1 = molecular weight of valganciclovir, 354.37

M_r2 = molecular weight of valganciclovir hydrochloride, 390.83

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, Sample stock solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.3 µg/mL of USP Valganciclovir Hydrochloride RS in Diluent prepared from the Standard solution in the Assay

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 3.0 between the two valganciclovir diastereomer peaks

Relative standard deviation: NMT 5.0% for the total areas of the two valganciclovir diastereomer peaks

Signal-to-noise ratio: NLT 10 each for the two valganciclovir diastereomer peaks

Analysis

Samples: Standard solution and Sample solution

[NOTE-The relative retention times for methoxymethylguanine, valganciclovir diester analog, isovalganciclovir peak 1, and isovalganciclovir peak 2 are 0.70, 1.54, 1.65, and 1.70, respectively.]

Calculate the percentage of any degradation product in the portion of Oral Solution taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × (1/F) × 100

r_u = peak response of any degradation product from the Sample solution

r_s = sum of the peak responses of the valganciclovir diastereomeric peaks from the Standard solution

C_s = concentration of USP Valganciclovir Hydrochloride RS in the Standard solution (mg/mL)

C_u = nominal concentration of valganciclovir in the Sample solution (mg/mL)

M_r1 = molecular weight of valganciclovir, 354.37

M_r2 = molecular weight of valganciclovir hydrochloride, 390.83

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard the peak due to fumaric acid at an RRT of about 0.30. The reporting threshold is 0.05%.

Table 2

a 2-Amino-1,9-dihydro-6H-purin-6-one.

b 2-Amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-1,9-dihydro-6H-purin-6-one.

6 SPECIFIC TESTS

pH 〈791〉: 2.0–3.8

Water Determination 〈921〉, Method I: NMT 8.0%

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 10² cfu/mL.

The total combined yeasts and molds count does not exceed 10¹ cfu/mL. It meets the requirements of the test for absence of Escherichia coli.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light and moisture. Store dry powder at controlled room temperature. Store constituted solution under refrigeration (2°–8°). Do not freeze.

USP Reference Standards 〈11〉

USP Valganciclovir Hydrochloride RS _{(USP 1-May-2024)}