A: Place a Tablet in a small beaker,crack the Tablet coating,add 10mLof methanol,and stir by mechanical means for about 10minutes.Allow to settle,and use the clear supernatant as the Test solution.Prepare a Standard solution in methanol containing about 20mg of USP Ibuprofen RSand 20Jmg of USP Pseudoephedrine Hydrochloride RSper mL,Jbeing the ratio of the labeled amount,in mg,of pseudoephedrine hydrochloride to the labeled amount,in mg,of ibuprofen per Tablet.Separately apply 10µLeach of the Test solutionand the Standard solution to a thin-layer chromatographic plate (see Chromatography á621ñ)covered with a 0.25-mm layer of chromatographic silica gel mixture and activated by heating the plate at 105for about 30minutes.Place the plate in a chromatographic chamber equilibrated with a solvent system consisting of a mixture of chloroform,methanol,and glacial acetic acid (80:15:5).Develop the chromatograms until the solvent has moved about 10cm from the origin.Remove the plate from the chromatographic chamber,place it in a chamber containing iodine vapors for about 10minutes,and examine the chromatograms:the principal spots obtained from the Test solutioncorrespond in RFvalue and appearance to those obtained from the Standard solution.

B: The retention times of the pseudoephedrine and ibuprofen peaks,relative to that of the butylparaben internal standard peak in the chromatogram of the Assay preparationcorrespond to those in the chromatogram of the Standard preparation,as obtained in the Assay.

Medium: pH7.2phosphate buffer (see under Buffersin the section Reagents,Indicators,and Solutions);900mL.

Apparatus 2: 50rpm.

Times: 30minutes (ibuprofen);45minutes (pseudoephedrine hydrochloride).

Procedure for ibuprofen— Determine the amount of ibuprofen (C13H18O2)dissolved from UVabsorbances at the wavelength of maximum absorbance at about 224nm of filtered portions of the solution under test,suitably diluted with Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Ibuprofen RSin the same medium.

Procedure for pseudoephedrine hydrochloride—

MOBILE PHASE— Prepare a solution of monobasic potassium phosphate in water containing 500mg per 1000mL.Filter through a filter having a porosity of 0.5µm or finer.Prepare a mixture of this solution and acetonitrile (500:500),and adjust with phosphoric acid to a pHof 3.3±0.1.Make any necessary adjustments (see System Suitabilityunder Chromatography á621ñ).Increasing the concentration of monobasic potassium phosphate or increasing the pHincreases the retention time of pseudoephedrine.

STANDARD PREPARATION —Prepare a solution of USP Pseudoephedrine Hydrochloride RSin Dissolution Mediumhaving a known concentration of about P/900mg per mL,Pbeing the labeled quantity,in mg,of pseudoephedrine hydrochloride per Tablet.

CHROMATOGRAPHIC SYSTEM (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 215-nm detector,a guard column containing packing L10,and a 4.6-mm ×25-cm column that contains packing L10.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor for the pseudoephedrine peak is not more than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%.

PROCEDURE— Pass a portion of the solution under test through a filter having a porosity of 0.5µm or finer.Separately inject equal volumes (about 10µL)of the filtrate and the Standard preparationinto the chromatograph,record the chromatograms,and measure the areas for the pseudoephedrine peaks.Calculate the quantity,in mg,of pseudoephedrine hydrochloride (C10H15NO·HCl)dissolved by the formula: in which Cis the concentration,in mg per mL,of USP Pseudoephedrine Hydrochloride RSin the Standard preparation,and rUand rSare pseudoephedrine peak responses obtained from the solution under test and the Standard preparation,respectively.

Tolerances— Not less than 75%(Q)of the labeled amounts of ibuprofen (C13H18O2)and pseudoephedrine hydrochloride (C10H15NO·HCl)are dissolved in 30minutes and in 45minutes,respectively.

Procedure for content uniformity— Proceed as directed in the Assay,preparing the Assay preparationas follows.Transfer 1Tablet to a glass-stoppered conical flask,add 10.0mLof Internal standard solution,and stir with a magnetic stirrer until the Tablet disintegrates.Add 10.0mLof acetonitrile,stir for about 15minutes,and filter.

Mobile phase— Dissolve 2.5g of docusate sodium in a mixture of water and acetonitrile (590:410).Add 1.0mLof phosphoric acid,and adjust with ammonium hydroxide to a pHof 3.2±0.05.Make any necessary adjustments (see System Suitabilityunder Chromatography á621ñ).Decreasing the proportion of docusate sodium increases the resolution between pseudoephedrine and ibuprofen.

Internal standard solution— Prepare a solution of butylparaben in Mobile phasecontaining about 0.15mg per mL.

Standard preparation— Prepare a solution in Internal standard solutionhaving known concentrations of about 20mg of USP Ibuprofen RSand 20Jmg of USP Pseudoephedrine Hydrochloride RSper mL,Jbeing the ratio of the labeled amount,in mg,of pseudoephedrine hydrochloride to the labeled amount,in mg,of ibuprofen per Tablet.To the resulting solution add an equal volume of acetonitrile,accurately measured,and mix.Filter through a filter of 0.5µm porosity or finer,and use the filtrate as the Standard preparation.This solution contains about 10mg of USP Ibuprofen RSand 10Jmg of USP Pseudoephedrine Hydrochloride RSper mL.

Assay preparation— Transfer an accurately counted number of Tablets,equivalent to about 2000mg of ibuprofen,to a glass-stoppered conical flask,add 100mLof Internal standard solution,and stir with a magnetic stirrer until the Tablets disintegrate.Add 100mLof acetonitrile,and mix.Filter through a filter of 0.5µm porosity or finer,and use the filtrate as the Assay preparation.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector,a guard column that contains packing L1,and a 4.6-mm ×10-cm column that contains 5-µm packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the relative retention times are about 0.55for butylparaben,0.7for pseudoephedrine,and 1.0for ibuprofen,the resolution,R,between the butylparaben peak and the pseudoephedrine peak and between the pseudoephedrine peak and the ibuprofen peak is not less than 2.0,the tailing factors for the butylparaben peak,the pseudoephedrine peak,and the ibuprofen peak are not more than 3.0,and the relative standard deviation for replicate injections determined from the peak response ratios is not more than 2.0%.

Procedure— Separately inject equal volumes (about 5µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantities,in mg,of ibuprofen (C13H18O2)and of pseudoephedrine hydrochloride (C10H15NO·HCl)in each Tablet taken by the formula: in which Cis the concentration,in mg per mL,of USP Ibuprofen RSor USP Pseudoephedrine Hydrochloride RS,as appropriate,in the Standard preparation,Nis the number of Tablets taken,and RUand RSare the ratios of the relevant analyte peak response to the butylparaben peak response obtained from the Assay preparationand the Standard preparation,respectively.