Valacyclovir 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

Valacyclovir Tablets contain an amount of Valacyclovir Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of valacyclovir (C₁₃H₂₀N₆O₄)

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.

B. IDENTIFICATION TESTS GENERAL, Chloride (191): Meet the requirements

3 ASSAY

PROCEDURE

Diluent: 0.1% (v/v) phosphoric acid in water

Mobile phase: Methanol and Diluent (5:95)

Standard solution: 0.1 mg/mL of USP Valacyclovir Hydrochloride RS in Diluent. [NOTE-USP Valacyclovir Hydrochloride RS contains a detectable quantity of D-valacyclovir.]

Sample solution: Transfer NLT 5 Tablets into a suitable volumetric flask, and add 0.1 M hydrochloric acid (approximately 80% of the volume of the flask). Mechanically shake the sample until the Tablets disintegrate into a fine suspension (60 min), and sonicate for 10 min. Cool to ambient temperature, dilute with 0.1 M hydrochloric acid to volume, and mix to obtain a solution having a concentration of 2.5 mg/mL. Dilute a portion of the sample with Diluent to obtain a nominal concentration of 0.1 mg/mL of valacyclovir, and mix. Pass a portion of this solution through a membrane filter of 0.45-um or finer pore size, and use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm x 15-cm; 5-µm packing L66

Column temperature: 10°

Flow rate: 0.75 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.3 between the D-valacyclovir and valacyclovir peaks

Tailing factor: NMT 2.0 for the valacyclovir peak

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valacyclovir (C₁₃H₂₀N₆O₄) in the portion of Tablets taken:

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

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

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

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

M_r1 = molecular weight of valacyclovir, 324.34

M_r2 = molecular weight of valacyclovir hydrochloride, 360.80

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Diluent: Prepare as directed in the Assay.

Mobile phase: Acetonitrile and Diluent (5:95)

Standard solution: Prepare a solution in Diluent containing USP Valacyclovir Hydrochloride RS equivalent to 0.044 mg/mL of valacyclovir free base.

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size. Dilute with Diluent to obtain a nal concentration of about 0.044 mg/mL of valacyclovir free base considering complete dissolution of the Tablet label claim.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 5-cm, 5-µm packing L1

Flow rate: 2.0 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valacyclovir (C₁₃H₂₀N₆O₄) dissolved:

Result = (r_u /r_s ) × C_s × V × (M_r1 /M_r2 ) × (1/L) × D × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

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

V = volume of Medium, 900 mL

M_r1 = molecular weight of valacyclovir, 324.34

M_r2 = molecular weight of valacyclovir hydrochloride, 360.80

L = label claim (mg/Tablet)

D = dilution factor of the Sample solution

Tolerances: NLT 75% (Q) of the labeled amount of valacyclovir (C₁₃H₂₀N₆O₄) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Analytical wavelength: 252 nm

Cell: 0.02 cm

Blank: Medium

Standard solution

For Tablets labeled to contain 500 mg: 0.6 mg/mL of USP Valacyclovir Hydrochloride RS in Medium. A small volume of methanol, not exceeding 5% of the nal volume, may be used to help solubilize valacyclovir.

For Tablets labeled to contain 1000 mg: 1.2 mg/mL of USP Valacyclovir Hydrochloride RS in Medium. A small volume of methanol, not exceeding 5% of the nal volume, may be used to help solubilize valacyclovir.

Sample solution: Pass a portion of the solution under test through a lter of 0.45-µm pore size. Discard the rst 3 mL of sample ltrate.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valacyclovir (C₁₃H₂₀N₆O₄) dissolved:

Result = (r_u /r_s ) × C_s × V × (M_r1 /M_r2 ) × (1/L) × D × 100

r_u = absorbance of the Sample solution

r_s = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

M_r1 = molecular weight of valacyclovir, 324.34

M_r2 = molecular weight of valacyclovir hydrochloride, 360.80

L = label claim (mg/Tablet)

D = dilution factor of the Sample solution

Tolerances: NLT 80% (Q) of the labeled amount of valacyclovir (C₁₃H₂₀N₆O₄) is dissolved.

Change to read:

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements _{(CN 1-Aug-2023)}

Procedure for content uniformity

[NOTE-All of the concentrations are expressed as valacyclovir free base.]

Diluent: Prepare as directed in the Assay.

Mobile phase: Acetonitrile and Diluent (5:95)

Standard solution: Prepare a solution of USP Valacyclovir Hydrochloride RS, equivalent to 0.04 mg/mL of valacyclovir, in Diluent,

Sample solution: Transfer 1 Tablet into a suitable volumetric flask. Add Diluent (approximately 60% of the volume of the flask), and mechanically shake the samples until the Tablet disintegrates into a fine suspension, and sonicate for 10 min. Cool, dilute with Diluent to volume, and mix. Dilute a portion of each sample with Diluent to obtain a nominal concentration of 0.04 mg/mL of valacyclovir. Pass a portion of each sample through a membrane filter of 0.45-µm pore size, and use the filtrate.

Chromatographic system and System suitability: Proceed as directed in Dissolution, Test 1.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of valacyclovir (C₁₃H₂₀N₆O₄) in the portion of Tablets taken:

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

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

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

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

M_r1 = molecular weight of valacyclovir, 324.34

M_r2 = molecular weight of valacyclovir hydrochloride, 360.80

_{(CN 1-Aug-2023)}

5 IMPURITIES

Organic Impurities

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of d-valacyclovir and Acyclovir 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 d-valacyclovir or acyclovir from the Sample solution

r_s = peak response of USP Valacyclovir Hydrochloride RS from the Standard solution

C_s = concentration of valacyclovir hydrochloride in the Standard solution (mg/mL)

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

M_r1 = molecular weight of valacyclovir, 324.34

M_r2 = molecular weight of valacyclovir hydrochloride, 360.80

F = relative response factor (see Table 1)

Acceptance criteria

Individual impurities: See Table 1.

Table 1

^a D-Valine, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy] ethyl ester, monohydrochloride. [Note—This is a process impurity.]

^b 2-Amino-9-[(2-hydroxyethoxy)methyl]-1,9-dihydro-6H-purin-6-one (acyclovir).

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉