A: Shake a quantity of powdered Tablets,equivalent to about 50mg of quinidine gluconate,with 100mLof dilute sulfuric acid (1in 350),and filter:the filtrate so obtained exhibits a vivid blue fluorescence when viewed under long-wavelength UVlight.On the addition of hydrochloric acid,the fluorescence disappears.

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.

C: In the test for Chromatographic purity,the RFvalue of the principal spot obtained from the Test preparationcorresponds to that from the Standard preparation.

TEST1— If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 1.

TEST4— If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 4.

TEST5— If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 5.

Procedure for content uniformity— Quantitatively transfer 1intact or powdered Tablet to a 250-mLvolumetric flask,and add about 125mLof 0.1Nhydrochloric acid.Heat the sample with frequent agitation just to boiling,and cool to room temperature.Dilute with 0.1Nhydrochloric acid to volume,mix,and filter,discarding the first 20mLof the filtrate.Concomitantly determine the absorbance of this solution,quantitatively diluted with 0.1Nhydrochloric acid,if necessary,and a Standard solution of USP Quinidine Gluconate RSin 0.1Nhydrochloric acid having a known concentration of about 0.0525mg per mL,in 1-cm cells,at the wavelength of maximum absorbance at about 347nm,with a suitable spectrophotometer,using 0.1Nhydrochloric acid as the blank.Calculate the quantity,in mg,of active ingredients,calculated as quinidine gluconate (C20H24N2O2·C6H12O7),in the Tablet taken by the formula: in which Tis the labeled quantity,in mg,of quinidine gluconate in the Tablet;Dis the concentration,in mg per mL,of quinidine gluconate in the solution from the Tablet,based on the labeled quantity per Tablet and the extent of dilution;Cis the concentration,in mg per mL,of USP Quinidine Gluconate RSin the Standard solution;and AUand ASare the absorbances of the solution from the Tablet and the Standard solution,respectively.

Standard solution— Prepare a solution of USP Quinidine Gluconate RSin diluted alcohol to contain 6mg per mL.

Diluted standard solution— Dilute a portion of the Standard solutionwith diluted alcohol to a concentration of 0.06mg per mL.

Quininone solution— Prepare a solution in diluted alcohol containing in each mL0.04mg of USP Quininone RS(corresponding to 0.06mg of the gluconate).

Test solution— Shake a quantity of powdered Tablets,equivalent to about 150mg of quinidine gluconate,with 25mLof diluted alcohol for 10minutes,and filter.

Procedure— Apply 10-µLportions of the Test solution,the Standard solution,the Diluted standard solution,and the Quininone solutionto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel.Allow to dry,and develop the chromatogram in a solvent system consisting of a mixture of chloroform,acetone,and diethylamine (5:4:1),the solvent chamber being used without previous equilibration.When the solvent front has moved about 15cm,remove the plate from the chamber,mark the solvent front,and allow the solvent to evaporate.Spray the chromatogram with glacial acetic acid.Locate the spots on the plate by examination under long-wavelength UVlight.Any spot produced by the Test solutionat the RFvalue of a spot produced by the Quininone solutionis not greater in size or intensity than that corresponding spot.Apart from these spots and from the spots appearing at the RFvalue of quinidine gluconate and dihydroquinidine gluconate (the two spots most evident from the Standard solution),any additional fluorescent spot is not greater in size or intensity than the principal spot of the Diluted standard solution.

Methanesulfonic acid solution— Add 35.0mLof methanesulfonic acid to 20.0mLof glacial acetic acid,dilute with water to 500mL,and mix.

Diethylamine solution— Dissolve 10.0mLof diethylamine in water to obtain 100mLof solution.

Mobile phase— Prepare a suitable filtered and degassed mixture of water,acetonitrile,Methanesulfonic acid solution,and Diethylamine solution (860:100:20:20).Adjust with Diethylamine solutionto a pHof 2.6if found to be lower.

System suitability preparation— Transfer about 10mg each of quinidine gluconate and dihydroquinidine chloride to a 50-mLvolumetric flask.Dissolve in about 5mLof methanol,dilute with Mobile phase to volume,and mix.

Standard preparation— Transfer about 20mg of USP Quinidine Gluconate RS,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 160mg of quinidine gluconate,to a 100-mLvolumetric flask,add about 80mLof a mixture of methanol and water (1:1),and sonicate until evenly dispersed.Cool to room temperature,dilute with a mixture of methanol and water (1:1)to volume,mix,and filter,discarding the first 20mLof the filtrate.Transfer 3.0mLof the filtrate to a 25-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 235-nm detector and a 3-to 5-mm ×25-to 30-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the typical relative retention times for quinidine and dihydroquinidine are 1and 1.5,respectively,and the resolution,R,between quinidine and dihydroquinidine peaks is not less than 1.2.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the quinidine and dihydroquinidine peaks.Calculate the quantity,in mg,of the sum of quinidine gluconate and dihydroquinidine gluconate in the portion of Tablets taken by the formula: in which Cis the concentration,in mg per mL,of USP Quinidine Gluconate RSin the Standard preparation;rb,Uand rb,Sare the peak responses of quinidine obtained from the Assay preparationand the Standard preparation,respectively;and rd,Uand rd,Sare the peak responses of dihydroquinidine obtained from the Assay preparationand the Standard preparation,respectively.