Quinidine Sulfate Capsules
»Quinidine Sulfate Capsules contain amounts of quinidine sulfate and dihydroquinidine sulfate totaling not less than 90.0percent and not more than 110.0percent of the labeled amount of quinidine sulfate,calculated as (C20H24N2O2)2·H2SO4·2H2O.
Packaging and storage Preserve in tight,light-resistant containers.
A: Shake a quantity of the contents of Capsules,equivalent to about 100mg of quinidine sulfate,with 10mLof dilute sulfuric acid (1in 350),and filter:an appropriate dilution of the filtrate exhibits a vivid blue fluorescence.On the addition of a few drops of hydrochloric acid the fluorescence disappears.
B: In the test for Chromatographic purity,the RFvalue of the principal spot obtained from the Test preparationcorresponds to that from the Standard preparation.
C: Shake a quantity of the contents of Capsules,equivalent to about 100mg of quinidine sulfate,with 10mLof dilute hydrochloric acid (1in 100),and filter:the filtrate responds to the tests for Sulfate á191ñ.
Medium: 0.01Nhydrochloric acid;900mL.
Apparatus 1: 100rpm.
Procedure Determine the amount of (C20H24N2O2)2·H2SO4·2H2Odissolved by employing UVabsorption at the wavelength of maximum absorbance at about 248nm on filtered portions of the solution under test,suitably diluted with Dissolution Medium,in comparison with a Standard solution having a known concentration of USP Quinidine Sulfate RSin the same Medium.
Tolerances Not less than 85%(Q)of the labeled amount of (C20H24N2O2)2·H2SO4·2H2Ois dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Procedure for content uniformity Transfer the contents of 1Capsule to a 250-mLvolumetric flask,add about 175mLof dilute hydrochloric acid (1in 100),and shake by mechanical means for 30minutes.Add dilute hydrochloric acid (1in 100)to volume,and mix.Filter a portion of the mixture,discarding the first 20mLof the filtrate.Concomitantly determine the absorbances of this solution,quantitatively diluted,if necessary,and a Standard solution of USP Quinidine Sulfate RSin dilute hydrochloric acid (1in 100)having a known concentration of about 40µg per mL,in 1-cm cells,at the wavelength of maximum absorbance at about 345nm,with a suitable spectrophotometer,using water as the blank.Calculate the quantity,in mg,of active ingredients,calculated as quinidine sulfate [(C20H24N2O2)2·H2SO4·2H2O],in the Capsule taken by the formula:
(TC/D)(AU/AS),in which Tis the labeled quantity,in mg,of quinidine sulfate in the Capsule,Dis the concentration,in µg per mL,of quinidine sulfate in the solution from the Capsule,based on the labeled quantity per Capsule and the extent of dilution,Cis the concentration,in µg per mL,of USP Quinidine Sulfate RSin the Standard solution,and AUand ASare the absorbances of the solution from the Capsule and the Standard solution,respectively.
Chromatographic purity Shake a quantity of the contents of Capsules,equivalent to about 150mg of quinidine sulfate,with 25mLof diluted alcohol for 10minutes,and filter.Using this as the test solution,proceed as directed in the test for Chromatographic purityunder Quinidine Sulfate.
Methanesulfonic acid solution,Diethylamine solution,Mobile phase,System suitability preparation,and System suitability test Proceed as directed for Limit of dihydroquinidine sulfateunder Quinidine Sulfate.
Standard preparation Transfer about 20mg of USP Quinidine Sulfate RS,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.
Assay preparation Transfer the contents of not less than 20Capsules to a container,and mix.Transfer an accurately weighed portion of the powder,equivalent to about 160mg of quinidine sulfate,to a 100-mLvolumetric flask,add 80mLof methanol,and shake the flask by mechanical means for 30minutes.Dilute with methanol to volume,mix,and filter,discarding the first 10mLof the filtrate.Transfer 3.0mLof the filtrate to a 25-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Procedure (see Chromatography á621ñ)Inject equal volumes (about 50µL)of the Standardand Assay preparationsinto a chromatograph equipped with a 235-nm detector and a 3.9-mm ×30-cm column that contains packing L1.Calculate the quantity,in mg,of the sum of quinidine sulfate and dihydroquinidine sulfate in the portion of Capsules taken by the formula:
(2500/3)C(rb,U+rd,U)/(rb,S+rd,S),in which Cis the concentration,in mg per mL,of USP Quinidine Sulfate 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.
Auxiliary Information Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5