A: Infrared Absorption á197Kñ—

Test specimen— Transfer a portion of finely powdered Tablets,equivalent to about 25mg of verapamil hydrochloride,to a separator.Add 25mLof water,and shake by mechanical means for 30minutes.Add 1mLof 1Nsodium hydroxide,and extract with 25mLof chloroform,shaking by mechanical means for 10minutes.Pass the chloroform extract through a filter containing anhydrous sodium sulfate.Triturate the chloroform extract with 400mg of potassium bromide and evaporate to dryness.Dry at 105for 2hours.

B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.

Medium: 0.01Nhydrochloric acid;900mL.

Apparatus 2: 50rpm.

Time: 30minutes.

Procedure— Determine the amount of C27H38N2O4·HCl dissolved from the difference between UVabsorbances at the wavelengths of maximum absorbance at about 278nm and 300nm using filtered portions of the solution under test,suitably diluted with Mediumif necessary,in comparison with a Standard solution having a known concentration of USP Verapamil Hydrochloride RSin the same Medium.

Tolerances— Not less than 75%(Q)of the labeled amount of C27H38N2O4·HCl is dissolved in 30minutes.

Procedure for content uniformity— Transfer 1Tablet to a 100-mLvolumetric flask,add 50mLof 0.01Nhydrochloric acid,and heat on a steam bath for 50minutes.Sonicate the heated solution for about 10minutes,cool,dilute with 0.01Nhydrochloric acid to volume,mix,and filter.Dilute an accurately measured portion of the filtrate quantitatively with 0.01Nhydrochloric acid to obtain a Test preparationcontaining about 48µg of verapamil hydrochloride per mL.Dissolve an accurately weighed quantity of USP Verapamil Hydrochloride RSin 0.01Nhydrochloric acid to obtain a Standard preparationhaving a known concentration of about 48µg per mL.Concomitantly determine the absorbances of the Test preparationand the Standard preparationin 1-cm cells at the wavelength of maximum absorbance at about 278nm and the absorbance of the Test preparationat 300nm,with a suitable spectrophotometer using 0.01Nhydrochloric acid as the blank.Calculate the quantity,in mg,of C27H38N2O4·HCl in the Tablet taken by the formula: in which Tis the labeled quantity,in mg,of verapamil hydrochloride in the Tablet;Cis the concentration,in µg per mL,of USP Verapamil Hydrochloride RSin the Standard preparation;Dis the concentration,in µg per mL,of verapamil hydrochloride in the Test preparation,on the basis of the labeled quantity per Tablet and the extent of dilution;AUis the difference between absorbances at 278nm and 300nm of the Test preparation;and ASis the absorbance of the Standard preparationat 278nm.

Aqueous solvent mixture ,Mobile phase,System suitability solution,and Chromatographic system—Proceed as directed in the test for Chromatographic purityunder Verapamil Hydrochloride.

Standard solution— Dissolve accurately weighed quantities of USP Verapamil Hydrochloride RS,USP Verapamil Related Compound A RS,3,4-dimethoxybenzaldehyde,and 3,4-dimethoxybenzyl alcohol in Mobile phaseto obtain a solution having known concentrations of about 1.6mg of USP Verapamil Hydrochloride RSper mLand 0.0048mg each of USP Verapamil Related Compound A RS,3,4-dimethoxybenzaldehyde,and 3,4-dimethoxybenzyl alcohol per mL.

Test solution— Use the Assay preparation.

Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,and allow the Test solutionto elute for not less than four times the retention time for verapamil.Record the chromatograms,and measure all of the peak responses.[NOTE—The retention times are about 0.4for 3,4-dimethoxybenzyl alcohol,0.5for verapamil related compound A,0.7for 3,4-dimethoxybenzaldehyde,and 1.0for verapamil.]Calculate the quantity,in mg,of each individual impurity in each mLof the portion of Tablets taken by the formula: in which Cis the concentration,in mg per mL,of the appropriate impurity in the Standard solution;and rUand rSare the peak responses of the appropriate impurity obtained from the Test solutionand the Standard solution,respectively:not more than 0.3%of any specified impurity is found;and the sum of all impurities is not more than 1.0%.

Aqueous solvent mixture ,Mobile phase,System suitability solution,and Chromatographic system—Proceed as directed in the test for Chromatographic purityunder Verapamil Hydrochloride.

Standard preparation— Dissolve an accurately weighed quantity of USP Verapamil Hydrochloride RSin Mobile phaseto obtain a solution having a known concentration of about 1.6mg per mL.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 40mg of verapamil hydrochloride,to a stoppered centrifuge tube,and add 25mLof Mobile phase.Shake by mechanical means for 15minutes,centrifuge,and if necessary filter the supernatant.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,and allow the Assay preparationto elute for not less than four times the retention time for verapamil.Record the chromatograms,and measure the responses for all of the major peaks.Calculate the quantity,in mg,of verapamil hydrochloride (C27H38N2O4·HCl)in the portion of Tablets taken by the formula: in which Cis the concentration,in mg per mL,of USP Verapamil Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.