» Simvastatin Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of simvastatin (C25H38O5).
Packaging and storage Preserve in tight containers.
USP Reference standards 11
Identification The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Medium: pH 7.0 buffer solution containing 0.5% sodium dodecyl sulfate in 0.01 M sodium phosphate prepared by dissolving 30 g of sodium dodecyl sulfate and 8.28 g of monobasic sodium phosphate in 6000 mL of water, and adjusting with 50% (w/v) sodium hydroxide solution to a pH of 7.0; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Prewashed manganese dioxide Transfer 10 g of manganese dioxide to a suitable container, and treat as follows. Add 50 mL of Dissolution Medium, and shake vigorously for 5 minutes. Centrifuge, decant the supernatant layer, and discard. Repeat twice, first with Dissolution Medium and then with water. Dry the solid at 100 for 1 hour before use.
Test solution Transfer a filtered portion of the solution under test to a centrifuge tube containing about 10 mg of Prewashed manganese dioxide per mL of transferred solution under test, and mix. Allow the mixture to stand for 30 minutes with occasional shaking, centrifuge, and use a portion of the clear supernatant as the Test solution.
Blank Proceed as directed for Test solution, except to use the Dissolution Medium.
Procedure Determine the amount of C25H38O5 dissolved from the difference between the UV absorbances at the wavelengths of maximum and minimum absorbance at about 247 nm and 257 nm, respectively, on filtered portions of the Test solution, in comparison with a Standard solution having a known concentration of USP Simvastatin RS in the same Medium treated in the same way as the solution under test, each solution corrected for the Blank.
Tolerances Not less than 75% (Q) of the labeled amount of C25H38O5 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Diluting solution Add 3.0 mL of glacial acetic acid to 900 mL of water. Adjust with 5 N sodium hydroxide to a pH of 4.0, and dilute with water to 1000 mL. To 200 mL of this solution, add 800 mL of acetonitrile, and mix.
Buffer solution Dissolve 3.9 g of monobasic sodium phosphate in 900 mL of water. Adjust, if necessary, with either 50% sodium hydroxide or 85% phosphoric acid to a pH of 4.5, dilute with water to 1000 mL, and mix.
Mobile phase Prepare a filtered and degassed mixture of acetonitrile and Buffer solution (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Dissolve an accurately weighed quantity of USP Simvastatin RS in Diluting solution, and dilute quantitatively, and stepwise if necessary, with Diluting solution to obtain a solution having a known concentration of about 0.1 mg per mL.
Assay preparation Transfer 10 Tablets to a 250-mL volumetric flask. Add a small volume of water (not more than 10 mL), and swirl to disintegrate the Tablets. Dilute with Diluting solution to volume, sonicate for 15 minutes, and cool to room temperature. If necessary, dilute with Diluting solution to volume. Centrifuge a portion of the mixture, and dilute a portion of the clear supernatant with Diluting solution to obtain a solution having a concentration of about 0.1 mg of simvastatin per mL.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 238-nm detector and a 4.6-mm × 25-cm column containing packing L1 and maintained at a temperature of 45. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, is not less than 3.0; the column efficiency is not less than 4500 theoretical plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas of the major peaks. Calculate the quantity, in mg, of simvastatin (C25H38O5) in each Tablet taken by the formula:
(L / D)C(rU / rS)in which L is the labeled quantity, in mg, of simvastatin in each Tablet; D is the concentration, in mg per mL, of simvastatin in the Assay preparation; C is the concentration, in mg per mL, of USP Simvastatin RS in the Standard preparation; and rU and rS are the peak areas of simvastatin obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 4641Pharmacopeial Forum: Volume No. 29(2) Page 437