A: Place a quantity of finely powdered Tablets,equivalent to about 40mg of metoprolol tartrate,in a separator,add 25mLof water and 4mLof dilute ammonium hydroxide (1in 3),and extract with 20mLof chloroform,filtering the chloroform extract through chloroform-prerinsed anhydrous sodium sulfate.Evaporate the chloroform to dryness,and place in a freezer to congeal the residue:the IRabsorption spectrum of a potassium bromide dispersion of the residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Metoprolol Tartrate RS.

B: Transfer a portion of finely powdered Tablets,equivalent to about 50mg of metoprolol tartrate,to a 500-mLvolumetric flask,dilute with water to volume,and mix.Pass a portion of this solution through a filter of 1µm or finer porosity:the UVspectrum of the filtrate exhibits maxima and minima at the same wavelengths as that of a solution of USP Metoprolol Tartrate RSin water having a concentration of about 0.1mg per mL.

C: The retention time of the metoprolol peak in the chromatogram obtained from the Assay preparationcorresponds to that in the chromatogram of the Standard preparationas obtained in the Assay.

Medium: simulated gastric fluid TS(without enzyme);900mL.

Apparatus 1: 100rpm.

Time: 30minutes.

Procedure— Determine the amount of (C15H25NO3)2·C4H6O6dissolved in filtered portions of the solution under test from UVabsorbances at the wavelength of maximum absorbance at about 275nm in comparison with a Standard solution having a known concentration of USP Metoprolol Tartrate RSin the same medium.

Tolerances— Not less than 75%(Q)of the labeled amount of (C15H25NO3)2·C4H6O6is dissolved in 30minutes.

Solvent mixture— Prepare a mixture of methanol and 0.1Nhydrochloric acid (1:1).

Mobile phase— Prepare a suitable and degassed solution by dissolving 961mg of 1-pentanesulfonic acid sodium salt (monohydrate)and 82mg of anhydrous sodium acetate in a mixture of 550mLof methanol and 470mLof water and adding 0.57mLof glacial acetic acid.

Standard preparation— Dissolve an accurately weighed quantity of USP Metoprolol Tartrate RSin Solvent mixtureto obtain a stock solution having a known concentration of about 1000µg per mL.Transfer 25.0mLof this solution to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Resolution solution— Prepare a solution of oxprenolol hydrochloride in Solvent mixtureto obtain a solution containing about 720µg per mL.Prepare a 1:1mixture of this solution and the stock solution used to prepare the Standard preparation.

Assay preparation— Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 50mg of metoprolol tartrate,to a 50-mLvolumetric flask,add 30mLof Solvent mixture,shake by mechanical means for 30minutes,sonicate for 15minutes,and heat on a steam bath for 10minutes.Allow the solution to cool to room temperature,dilute with Solvent mixtureto volume,and mix.Centrifuge a portion of the solution,and transfer 25.0mLof the supernatant to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Pass a portion of this solution through a filter of 0.5µm or finer porosity,discarding the first few mLof the filtrate.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed under Procedure:the relative retention times are about 0.8for metoprolol and 1.0for oxprenolol,and the resolution,R,between the metoprolol and oxprenolol peaks is not less than 2.0.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%.

Procedure— Separately inject equal volumes (about 30µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of metoprolol tartrate [(C15H25NO3)2·C4H6O6]in the portion of Tablets taken by the formula: in which Cis the concentration,in µg per mL,of USP Metoprolol Tartrate RSin the Standard preparation;and rUand rSare the metoprolol peak responses obtained from the Assay preparationand the Standard preparation,respectively.