Valganciclovir Tablets

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 Tablets contain NLT 93.0% and NMT 105.0% of the labeled amount of valganciclovir (C₁₄H₂₂N₆O₅).

2 IDENTIFICATION

Change to read:

A. ASPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 197U _{(CN 1-MAY-2020)}

Sample solution: 10 µg/mL in 0.001 M hydrochloric acid

Wavelength range: 200-350 nm

Medium: 0.001 M hydrochloric acid

Acceptance criteria: Meet the requirements

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

3 ASSAY

PROCEDURE

Buffer: Dilute 2.5 mL of triethylamine with water to 1000 mL, and adjust with trifluoroacetic acid to a pH of 3.0 ± 0.05.

Mobile phase: Methanol and Buffer (7:93)

Diluent: 1 mM hydrochloric acid

System suitability solution: 0.1 µg/mL of USP Ganciclovir Mono-N-methyl Valinate RS and 78 µg/mL of USP Valganciclovir Hydrochloride RS in Diluent

Standard solution: 0.09 mg/mL of USP Valganciclovir Hydrochloride RS in Diluent. Pass a portion of the solution through a filter of 0.45-µm or finer pore size, and use the filtrate, discarding the initial 2 mL.

Sample stock solution: Nominally 5 mg/mL of valganciclovir hydrochloride prepared as follows. Transfer 5 Tablets into a 500-mL volumetric flask, add about 300 mL of Diluent, and shake well until the Tablets are fully disintegrated. Dilute with Diluent to volume, mix, and allow the solution to settle.

Sample solution: Nominally 0.075 mg/mL of valganciclovir hydrochloride prepared as follows. Transfer 3.0 mL of the supernatant from the Sample stock solution into a 200-mL volumetric flask, and dilute with Diluent to volume. Pass a portion of this solution through a filter of 0.45-µm or finer pore size, and use the filtrate, discarding the initial 2 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; packing L11

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between the second diastereomeric valganciclovir peak and the rst ganciclovir mono-N-methyl valinate peak, System suitability solution

Column eciency: NLT 3000 theoretical plates for the second diastereomeric valganciclovir peak, Standard solution

Tailing factor: NMT 3 for the second diastereomeric valganciclovir peak, Standard solution

Relative standard deviation: NMT 2.0% for the total areas of the two valganciclovir peaks, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valganciclovir (C₁₄H₂₂N₆O₅) in the portion of Tablets 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 diastereomers from the Sample solution

r_s = sum of the peak responses of the valganciclovir diastereomers from the Standard solution

C_s = concentration of USP Valganciclovir Hydrochloride RS in the Standard solution, corrected for water content (mg/mL)

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

M_r1 = molecular weight of valganciclovir, 354.36

M_r2 = molecular weight of valganciclovir hydrochloride, 390.82

Acceptance criteria: 93.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL, deaerated

Apparatus 2: 50 rpm

Time: 30 min

Standard stock solution: 5 mg/mL of valganciclovir in Medium. Expose the USP Valganciclovir Hydrochloride RS to ambient conditions overnight, and determine the water content before use.

Standard solution: 0.5 mg/mL of valganciclovir in Medium from the Standard stock solution. Pass a portion of this solution through a polyethylene lter of 10-µm pore size, discarding the rst 2 mL of the ltrate.

Sample solution: Pass 10 mL of the solution under test through a polyethylene lter of 10-µm pore size, discarding the rst 2 mL of the ltrate. Suitably dilute with Medium, if necessary, in comparison with the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: Absorption maximum at about 254 nm

Cell length: 0.02 cm quartz cell

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valganciclovir (C₁₄H₂₂N₆O₅) dissolved:

Result = (A_u /A_s ) × (C_s /L) × V × (M_r1 /M_r2 ) × D × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Valganciclovir Hydrochloride RS in the Standard solution, corrected for water content (mg/mL)

L = label claim of valganciclovir (mg/Tablet)

V = volume of Medium, 900 mL

M_r1 = molecular weight of valganciclovir, 354.36

M_r2 = molecular weight of valganciclovir hydrochloride, 390.82

D = dilution factor

Tolerances: NLT 80% (Q) of the labeled amount of valganciclovir (C₁₄H₂₂N₆O₅) is dissolved.

Uniformity of Dosage Units 〈905〉

Procedure for content uniformity

Mobile phase, Diluent, System suitability solution, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample solution: Transfer 1 Tablet to a 100-mL volumetric ask, add about 80 mL of Diluent, and sonicate until the Tablet is fully disintegrated. Dilute with Diluent to volume, mix, and allow the solution to settle. Pipet 3.0 mL of the top portion of the resulting solution into a 200-mL volumetric ask, and dilute with Diluent to volume. Pass a portion of the solution through a lter of 0.45-µm or ner pore size, and use the ltrate, discarding the initial 2 mL.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of valganciclovir (C₁₄H₂₂N₆O₅) in the Tablet 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 diastereomers from the Sample solution

r_s = sum of the peak responses of the valganciclovir diastereomers from the Standard solution

C_s = concentration of USP Valganciclovir Hydrochloride RS in the Standard solution, corrected for water content (mg/mL)

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

M_r1 = molecular weight of valganciclovir, 354.36

M_r2 = molecular weight of valganciclovir hydrochloride, 390.82

Acceptance criteria: Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Mobile phase, Diluent, System suitability solution, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample solution: Nominally 0.45 mg/mL of valganciclovir prepared as follows. Transfer an equivalent to 450 mg of valganciclovir from finely powdered Tablets (NLT 20) to a 1000-mL volumetric flask. Add about 800 mL of Diluent, and sonicate until the solid sample is fully disintegrated. Dilute with Diluent to volume. Pass a portion of this solution through a filter of 0.45-µm or finer pore size, and use the filtrate, discarding the initial 2 mL.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ganciclovir and guanine in the portion of Tablets taken:

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

r_u = peak response of ganciclovir or guanine from the Sample solution

r_s = sum of the peak responses of the valganciclovir diastereomers from the Standard solution

C_s = concentration of USP Valganciclovir Hydrochloride RS in the Standard solution, corrected for water content (mg/mL)

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

M_r1 = molecular weight of valganciclovir, 354.36

M_r2 = molecular weight of valganciclovir hydrochloride, 390.82

F = relative response factor (see Table 1)

Calculate the percentage of each individual unidentied and identied impurity in the portion of Tablets taken:

Result = (r_u /r_t ) × 100

r_u = peak response of each impurity from the Sample solution

r_t = sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 1.

Table 1

^a Degradant.

^b Impurity.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at 25°, excursions permitted between 15° and 30°.

USP Reference Standards 〈11〉

USP Ganciclovir Mono-N-methyl Valinate RS

2-(RS)-[(Guanin-9-yl)methoxy]-3-hydroxypropyl N-methyl-l-valinate.

C₁₅H₂₄N₆O₅      368.39

USP Valganciclovir Hydrochloride RS