Valganciclovir Tablets
» Valganciclovir Tablets contain not less than 93.0 percent and not more than 105.0 percent of the labeled amount of valganciclovir (C14H22N6O5).
Packaging and storage— Preserve in tight containers. Store at 25, excursions permitted between 15 and 30.
USP Reference standards 11
USP Valganciclovir Hydrochloride RS Click to View Structure
USP Ganciclovir Mono-N-Methyl Valinate RS
2-(RS)-[(Guanin-9-yl]methoxy)-3-hydroxypropyl N-methyl-l-valinate.
    C15H24N6O5     368.39
Identification—
A: Ultraviolet Absorption 197U
Spectral range: 200–350 nm.
Solution: 10 µg per mL.
Medium: 0.001 M hydrochloric acid.
B: The retention time of the diastereomeric peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: 0.1 N hydrochloric acid; 900 mL, deaerated.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Standard solution— Expose the USP Valganciclovir Hydrochloride RS to ambient conditions overnight, and determine the water content prior to use. Accurately weigh an amount, equivalent to about 100 mg of valganciclovir free base, transfer to a 20-mL volumetric flask, dilute with Medium to volume, and mix.
Working standard solution— Transfer 5.0 mL of the Standard solution to a 50-mL volumetric flask, dilute with Medium to volume, and mix well. Pass a portion of this solution through a 10-µm polyethylene filter, discarding the first 2 mL of the filtrate.
Test solution— Pass 10 mL of the solution under test through a 10-µm polyethylene filter, discarding the first 2 mL of the filtrate.
Procedure— Determine the amount of C14H22N6O5 dissolved by UV absorption at the wavelength of maximum absorbance at about 254 nm on portions of the Test solution, suitably diluted with Medium, if necessary, in comparison with the Working standard solution, using a 0.02-cm quartz cell. Calculate the weight of valganciclovir free base using the formula:
Click to View Image
in which WS is the weight, in mg, of USP Valganciclovir Hydrochloride RS taken to prepare the Standard solution; WC is the water content of USP Valganciclovir Hydrochloride RS; 0.91 is the conversion factor from valganciclovir hydrochloride to valganciclovir free base; and P is the purity, in decimals, of USP Valganciclovir Hydrochloride RS. Calculate the amount, in percentage, of valganciclovir released using the formula:
Click to View Image
in which AU and AS are the absorbances obtained from the Test solution and the Working standard solution, respectively; CS is the concentration, in mg per mL, of valganciclovir free base in the Working standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Tolerances— Not less than 80% (Q) of the labeled amount of valganciclovir is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
procedure for content uniformity—
Mobile phase, Diluent, Resolution solution, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Prepare as directed for the Standard preparation in the Assay.
Test solution— Transfer 1 Tablet to a 100-mL volumetric flask, 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 flask, dilute with Diluent to volume, and mix. Pass a portion of the solution through a filter having a 0.45-µm or finer porosity, and use the filtrate, discarding the initial 2 mL.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of valganciclovir (C14H22N6O5) in the portion of Tablets taken by the formula:
WS (rU / rS)(0.91)(100 – SS /100)(DU / DS)
in which WS is the weight, in mg, of USP Valganciclovir Hydrochloride RS taken to prepare the Standard solution; rU and rS are the sums of the peak responses of valganciclovir obtained from the Test solution and the Standard solution, respectively; 0.91 is the conversion factor for valganciclovir hydrochloride to valganciclovir free base; SS is the percent of water in USP Valganciclovir Hydrochloride RS; and DU and DS are the dilution factors of the Test solution and the Standard solution, respectively.
Related compounds—
Mobile phase, Diluent, Resolution solution, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Use the Standard preparation in the Assay.
Test solution— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 450 mg of valganciclovir, to a 1000-mL volumetric flask, add about 800 mL of Diluent, and sonicate until the Tablet is fully disintegrated. Dilute with Diluent to volume, and mix. Pass a portion of this solution through a filter having a 0.45-µm or finer porosity, and use the filtrate, discarding the initial 2 mL.
Procedure— Inject a volume (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatogram, and measure all of the peak responses. Calculate the percentage of ganciclovir and guanine in the portion of Tablets taken by the formula:
WS (rU / rS)(0.91)(1/FL)(100 – SS /100)(DU /DS)(WA /WU)(100)
in which WS is the weight, in mg, of USP Valganciclovir Hydrochloride RS taken to prepare the Standard solution; rU is the guanine or ganciclovir peak response obtained from the Test solution; rS is the sum of the peak responses of the valganciclovir diastereomers obtained from the Standard solution; 0.91 is the conversion factor for valganciclovir hydrochloride to valganciclovir free base; F is the relative response factor, 1.9 and 1.4, for guanine and ganciclovir, respectively; L is the labeled amount, in mg, of valganciclovir in each Tablet; SS is the percent of water in USP Valganciclovir Hydrochloride RS; DU and DS are the dilution factors of the Test solution and the Standard solution, respectively; WA is the average weight, in mg, of a Tablet; and WU is the weight, in mg, of the powdered Tablet taken to prepare the Test solution. Not more than 2.0% of ganciclovir and not more than 1.0% of guanine are found.
Calculate the individual unidentified and identified impurities listed in Table 1 using the formula:
100(ri / rs)
in which ri is the peak response for each impurity/degradant, and rs is the sum of the responses of all the peaks: not more than 0.2% of each unidentified individual impurity is found; not more than 0.5% of total unidentified impurities/degradants is found; and not more than 3.5% of total impurities including all the degradation products is found.
Table 1
Name Component Approximate
Relative
Retention Time
Guanine Degradant 0.51
Ganciclovir Degradant 0.66
Valganciclovir 1 Active 1.00
Valganciclovir 2 Active 1.07
Ganciclovir-mono-N-
methyl valinate 1
Impurity 1.21
Ganciclovir-mono-N-
methyl valinate 2
Impurity 1.30
Methoxymethylguanine Impurity 1.45
Isovalganciclovir 1 Impurity 1.55
Isovalganciclovir 2 Impurity 1.61
Ganciclovir divalinate Impurity 2.13
Monoacetoxyganciclovir Impurity 2.31
Isomonochloroganciclovir Impurity 2.52
Homologue 1 Impurity 2.69
Homologue 2 Impurity 2.77
Assay—
Solution A— Dilute 2.5 mL of triethylamine with water to 1000 mL, and adjust with trifluoroacetic acid to a pH of 3.0 ± 0.05.
Solution B— Use methanol.
Mobile phase— Prepare a filtered and degassed mixture of Solution A and Solution B (93:7). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent— Dilute 1.0 mL of 1 M hydrochloric acid with water to 1.0 L, and mix.
Resolution solution— Dissolve suitable quantities of USP Ganciclovir mono-N-methyl Valinate RS and USP Valganciclovir Hydrochloride RS in Diluent to obtain a solution containing about 0.1 µg per mL and 78 µg per mL, respectively.
Standard stock preparation— Dissolve an accurately weighed quantity of USP Valganciclovir Hydrochloride RS, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.3 mg per mL.
Standard preparation— Pipet 6.0 mL of the Standard stock preparation into a 20-mL volumetric flask. Dilute with Diluent to volume, and mix well. Pass a portion of the solution through a filter having a 0.45-µm or finer porosity, and use the filtrate, discarding the initial 2 mL.
Assay preparation— 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. Transfer 3.0 mL of the supernatant into a 200-mL volumetric flask, and dilute with Diluent to volume. Pass a portion of this solution through a filter having a 0.45-µm or finer porosity, and use the filtrate, discarding the initial 2 mL.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm×15-cm column that contains packing L11. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 30. Chromatograph the Resolution solution as directed for Procedure: the resolution, R, between the second diastereomeric valganciclovir peak and the first ganciclovir mono-N-methyl valinate peak is not less than 2. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency for the second diastereomeric valganciclovir peak is not less than 3000 theoretical plates; the tailing factor for the second diastereomeric valganciclovir peak is not more than 3; and the relative standard deviation for the total areas for the two valganciclovir peaks for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of valganciclovir (C14H22N6O5) in the portion of Tablets taken by the formula:
WS (rU / rS)(0.91)(100 – SS /100)(DU / DS)
in which WS is the weight, in mg, of USP Valganciclovir Hydrochloride RS taken to prepare the Standard preparation; rU and rS are the sums of the peak responses for the valganciclovir diastereomers obtained from the Assay preparation and the Standard preparation, respectively; 0.91 is the conversion factor for valganciclovir hydrochloride to valganciclovir free base; SS is the percent of water in USP Valganciclovir Hydrochloride RS; and DU and DS are the dilution factors of the Assay preparation and the Standard preparation, respectively.
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(GCDF2010) General Chapters - Dosage Forms
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