A: Visualizing solution—In a 100-mLvolumetric flask dissolve 3g of bismuth subnitrate and 30g of potassium iodide with 10mLof 3Nhydrochloric acid.Dilute with water to volume,and mix.Prior to use,transfer 10.0mLof solution to a 100-mLvolumetric flask,add 10mLof 3Nhydrochloric acid,dilute with water to volume,and mix.

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

Apparatus 2: 50rpm.

Time: 20minutes.

Standard solution— Dissolve an accurately weighed quantity of USP Nifedipine RSin an amount of methanol not exceeding 2%of the final volume,and dilute quantitatively and stepwise,if necessary,with Dissolution Mediumto obtain a solution having a known appropriate concentration.

Procedure— Determine the amount of C17H18N2O6dissolved by employing UVabsorption at the wavelength of maximum absorbance at about 340nm on filtered portions of the solution under test,suitably diluted with Dissolution Medium,if necessary,in comparison with the Standard solution.[NOTE—Filters must be checked for absorptive loss of nifedipine.]

Tolerances— Not less than 80%(Q)of the labeled amount of C17H18N2O6is dissolved in 20minutes.

Procedure for content uniformity— With the point of a pair of sharp scissors,make a small hole at the end of 1Capsule.Squeeze most of the contents into a 200-mLvolumetric flask,cut the capsule in half,and drop it into the flask.Rinse the scissors with about 20mLof methanol,quantitatively collecting the rinse in the flask.Dilute with methanol to volume,and mix to obtain the test solution.Dissolve an accurately weighed quantity of USP Nifedipine RSin methanol,and dilute quantitatively and stepwise with methanol to obtain a Standard solution having a known concentration of about 50µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 350nm,with a suitable spectrophotometer,using methanol as the blank.Calculate the quantity,in mg,of nifedipine (C17H18N2O6)in the Capsule by the formula: in which Tis the labeled quantity,in mg,of nifedipine in the Capsule;Dis the concentration,in µg per mL,of nifedipine in the solution from the Capsule,on the basis of the labeled quantity per Capsule and the extent of dilution;Cis the concentration,in µg per mL,of USP Nifedipine RSin the Standard solution;and AUand ASare the absorbances of the solution from the Capsule and the Standard solution,respectively.

Mobile phase— Prepare as directed in the Assayunder Nifedipine.

Standard nifedipine solution— Prepare as directed for Standard nifedipine solutionin the test for Related compoundsunder Nifedipine.

Reference solution 1— Prepare as directed for Reference solution 1in the test for Related compoundsunder Nifedipine,except to make the final known concentration of about 6µg per mL.

Reference solution 2— Prepare as directed for Reference solution 2in the test for Related compoundsunder Nifedipine,except to make the final known concentration of about 1.5µg per mL.

Standard solution— Transfer 5.0mLof each of the two Reference solutionsto a container,add 5.0mLof Mobile phase,and mix.

Test solution— Prepare as directed for the Assay preparationin the Assay.

System suitability solution— Mix equal volumes of the Standard nifedipine solutionand of each of the two Reference solutions.

Chromatographic system— Prepare as directed in the Assay.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the resolution,R,between the nitrophenylpyridine analog and nitrosophenylpyridine analog peaks is not less than 1.5;the resolution,R,between the nitrosophenylpyridine analog and nifedipine peaks is not less than 1.0;and the relative standard deviation determined from the response for each analog in replicate injections is not more than 10%.The relative retention times are about 0.8for the nitrophenylpyridine analog,about 0.9for the nitrosophenylpyridine analog,and 1.0for nifedipine.

Procedure— Separately inject equal volumes (about 25µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of each related compound in the portion of Capsules taken by the formula: in which Vis the volume,in mL,of the Test solution,Cis the concentration,in mg per mL,of the appropriate USP Nifedipine Analog RSin the Standard solution;and rUand rSare the peak responses of the corresponding related compound obtained from the Test solutionand the Standard solution,respectively:not more than 2.0%of dimethyl 4-(2-nitrophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate,corresponding to nifedipine nitrophenylpyridine analog,and not more than 0.5%of dimethyl 4-(2-nitrosophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate,corresponding to nifedipine nitrosophenylpyridine analog,both relative to the nifedipine content,are found.

Mobile phase and Standard preparation— Prepare as directed in the Assayunder Nifedipine.

Assay preparation— Transfer the contents of 5Capsules with the aid of a small amount of methanol to a volumetric flask,quantitatively dilute with Mobile phaseto obtain a total volume,VmL,of solution having a concentration of about 0.1mg of nifedipine per mL.Pass through a solvent-resistant filter.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 265-nm detector,a 4.6-mm ×25-cm column that contains 5-µm packing L1,and a guard column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 4000theoretical plates;the tailing factor is not more than 1.5;and the relative standard deviation for replicate injections is not more than 1.0%.

Procedure— Separately inject equal volumes (about 25µL)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 nifedipine (C17H18N2O6)in each Capsule taken by the formula: in which Vis the volume,in mL,of the Assay preparation;Cis the concentration,in mg per mL,of USP Nifedipine RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.