Valacyclovir Tablets
DEFINITION
Valacyclovir Tablets contain an amount of Valacyclovir Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of valacyclovir (Cl3H20N6O4).
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
:
Meets the requirements
191:
Meets the requirements
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 volumetric 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-µm or finer pore size, and use the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4-mm × 15-cm; 5-µm packing L66
Column temperature:
10
Flow rate:
0.75 mL/min
Injection size:
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 C13H20N6O4, based on the label claim, in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Valacyclovir Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of valacyclovir in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of valacyclovir, 324.34 |
| Mr2 | = | = molecular weight of valacyclovir hydrochloride, 360.80 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
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 0.45-µm filter. Dilute with Diluent to obtain a final concentration of about 0.044 mg/mL of valacyclovir free base considering complete dissolution of the Tablet label claim.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 5-cm, 5-µm packing L1
Flow rate:
2.0 mL/min
Injection size:
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 valacyclovir dissolved:
Result = (rU/rS) × (CS) × (Mr1/Mr2) × (1/L) × 100 × 900
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of valacyclovir in the Standard solution (mg/mL) |
| Mr1 | = | = molecular weight of valacyclovir, 324.34 |
| Mr2 | = | = molecular weight of valacyclovir hydrochloride, 360.80 |
| L | = | = label claim (mg/Tablet) |
Tolerances:
NLT 75% (Q) of the labeled amount of valacyclovir is released
• Uniformity of Dosage Units 905:
Meets the requirements. [Note—All of the concentrations are expressed as valacyclovir free base. ]
905:
Meets the requirements. [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 one 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 0.45-µm membrane filter, and use the filtrate.
Chromatographic system and System suitability:
Proceed as directed under Dissolution.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C13H20N6O4, based on the label claim, in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Valacyclovir Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of valacyclovir in the Sample solution (mg/mL) |
IMPURITIES
Organic Impurities
• Procedure
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 = (rU/rS) × (CS/CU) × (Mr1/Mr2) × (1/F) × 100
| rU | = | = peak response of d-valacyclovir or acyclovir from the Sample solution |
| rS | = | = peak response of USP Valacyclovir Hydrochloride RS from the Standard solution |
| CS | = | = concentration of valacyclovir hydrochloride in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of valacyclovir in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of valacyclovir, 324.34 |
| Mr2 | = | = molecular weight of valacyclovir hydrochloride, 360.80 |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| d-Valacyclovira | 0.82 | 1.0 | — |
| Acyclovirb | 0.56 | 1.4 | 2.5 |
|
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).
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Valacyclovir Hydrochloride RS 
') + '&img=../../images/v35300/cas-124832-27-5.gif',600,500);)
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Leonel M. Santos, Ph.D.
Senior Scientific Liaison 1-301-816-8168 |
(SM12010) Monographs - Small Molecules 1 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4985
Pharmacopeial Forum: Volume No. 36(3) Page 689