Butanoic acid, 2,2-dimethyl-, 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester, [1S-[1,3,7,8(2S*,4S*),8a]].
2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-2-[(1S,2S,6R,8S,8R)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one [79902-63-9].
» Simvastatin contains not less than 98.0 percent and not more than 102.0 percent of C25H38O5, calculated on the dried basis. It may contain a suitable antioxidant.
Packaging and storage Preserve in well-closed containers. Store between 15 and 30, or under refrigeration.
B: 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.
Specific rotation 781S: between +285 and +298.
Test solution: 5 mg per mL, in acetonitrile.
Loss on drying 731 Dry it in vacuum at 60 for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.002%.
Chromatographic purity [noteThe Simvastatin solutions are stable for up to 3 days when stored at 4. Without refrigeration, they should be injected immediately after preparation.]
Mobile phase, Diluent, and Chromatographic system Proceed as directed in the Assay.
Test solution Use the Assay preparation.
Procedure Inject about 5 µL of the Test solution into the chromatograph, record the chromatogram, identify the specified impurities listed in Table 1, and measure the areas for all the peaks. Calculate the percentage of each impurity in the portion of Simvastatin taken by the formula:
100(ri / rs)in which ri is the peak area for each impurity; and rs is the sum of the areas of all the peaks. Reporting level for impurities is 0.05%.
Assay [noteThe Simvastatin solutions are stable for up to 3 days when stored at 4. Without refrigeration, they should be injected immediately after preparation.]
Dilute phosphoric acid Transfer 1 mL of phosphoric acid to a 1-L volumetric flask, and dilute with water to volume.
Solution A Prepare a mixture of acetonitrile and Dilute phosphoric acid (50:50).
Solution B Transfer 1 mL of phosphoric acid to a 1-L volumetric flask, and dilute with acetonitrile to volume.
Mobile phase Use variable mixtures of Solution A and Solution B, as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Buffer solution Prepare a solution containing 1.4 g of monobasic potassium phosphate per L, and adjust with phosphoric acid to a pH of 4.0.
Diluent Prepare a mixture of acetonitrile and Buffer solution (3:2).
System suitability preparation Dissolve accurately weighed quantities of USP Simvastatin RS and USP Lovastatin RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having known concentrations of about 1.5 mg per mL of USP Simvastatin RS and 0.015 mg per mL of USP Lovastatin RS.
Standard preparation Dissolve an accurately weighed quantity of USP Simvastatin RS in Diluent to obtain a solution having a known concentration of about 1.5 mg per mL.
Assay preparation Transfer about 75 mg of Simvastatin, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621 The liquid chromatograph is equipped with a 238-nm detector and a 4.6- × 33-mm column that contains packing L1. The flow rate is about 3.0 mL per minute. The chromatograph is programmed as follows.
Procedure Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C25H38O5 in the portion of Simvastatin taken by the formula:
VC(rU / rS)in which V is the volume, in mL, of 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 responses of the simvastatin peak obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.Chromatographic Column
USP32NF27 Page 3557Pharmacopeial Forum: Volume No. 33(5) Page 948
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.