A: Infrared Absorption á197Mñ.

B: Ultraviolet Absorption á197Uñ—

Solution: 10µg per mL.

Medium: acetonitrile.

Test solution: 5mg per mL,in acetonitrile.

Diluting solution— Prepare a solution of butylated hydroxytoluene in acetonitrile containing 0.5mg per mL.

Standard solutions— Dissolve an accurately weighed quantity of USP Simvastatin RSin Diluting solutionto obtain Standard solution Ahaving a known concentration of about 0.2mg per mL.Transfer 4.0,2.0,and 1.0mLof Standard solution Ato separate 10-mLvolumetric flasks,and dilute with Diluting solutionto volume to obtain Standard solutions B,C,and D,respectively.

Test solution— Dissolve an accurately weighed quantity of simvastatin in Diluting solutionto obtain a solution having a concentration of about 20mg per mL.

Procedure— Separately apply 4-µLportions of each of the Standard solutionsand the Test solutionto a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of silica gel mixture,previously washed with methanol and air-dried.Dry the spots with the aid of a stream of nitrogen.Position the plate in a chromatographic chamber previously equilibrated with a solvent system consisting of a mixture of cyclohexane,chloroform,and isopropyl alcohol (5:2:1)containing 0.5mg of butylated hydroxytoluene per mL,and develop the chromatogram until the solvent front has moved about three-quarters of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate under a stream of nitrogen.Spray the plate with a mixture of methanol and sulfuric acid (8:2),heat at 110for 30minutes,and immediately examine the plate:no secondary spot in the chromatogram of the Test solutionis greater in size or intensity than the principal spot from Standard solution B(0.4%),and the sum of all such secondary spots obtained from the Test solutionis not greater than 1.0%.

10,000(C/W)(ri/rS),

Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and dilute phosphoric acid (1in 1000)(50:50).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Diluting solution— Prepare a mixture of acetonitrile and 0.01Mmonobasic potassium phosphate (60:40),filter,and adjust with phosphoric acid to a pHof 4.0.

Standard preparation— Dissolve accurately weighed quantities of USP Simvastatin RSand USP Lovastatin RSin Diluting solution,and dilute quantitatively,and stepwise if necessary,to obtain a solution having known concentrations of about 0.3mg per mLof USP Simvastatin RSand 0.003mg per mLof USP Lovastatin RS.

Assay preparation— Transfer about 30mg of Simvastatin,accurately weighed,to a 100-mLvolumetric flask,and dissolve in and dilute with Diluting solutionto volume.

Chromatographic system (see Chromatography á621ñ)—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 3.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.65for lovastatin and 1.0for simvastatin,the resolution,R,between simvastatin and lovastatin is not less than 3.0,the column efficiency is not less than 2000theoretical plates,the tailing factor is not more than 2.0,and the relative standard deviation for replicate injections is not more than 1.0%.

Procedure— Separately inject equal volumes (about 5µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas of the responses for the major peaks.Calculate the quantity,in mg,of C25H38O5in the portion of Simvastatin taken by the formula: in which Cis the concentration,in mg per mL,of USP Simvastatin RSin the Standard preparation,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.