Quinidine Sulfate
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(C20H24N2O2)2·H2SO4·2H2O 782.94

Cinchonan-9-ol,6¢-methoxy-,(9S)-,sulfate (2:1)(salt),dihydrate.
Quinidine sulfate (2:1)(salt)dihydrate [6591-63-5].

Anhydrous 746.93 [50-54-4].
»Quinidine Sulfate is the sulfate of an alkaloid obtained from various species of Cinchonaand their hybrids and from Remijia pedunculataFlückiger (Fam.Rubiaceae),or prepared from quinine.It contains not less than 99.0percent and not more than 101.0percent of total alkaloid salt,calculated as (C20H24N2O2)2·H2SO4,on the anhydrous basis.
Packaging and storage— Preserve in well-closed,light-resistant containers.
A: A1in 2000solution in dilute sulfuric acid (1in 350)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: A1in 50solution made with the aid of a few drops of hydrochloric acid responds to the tests for Sulfate á191ñ.
Specific rotation á781ñ: between +275and +288,calculated on the anhydrous basis,determined in a solution in 0.1Nhydrochloric acid containing 200mg in each 10mL.
Water,Method Iá921ñ: between 4.0%and 5.5%.
Residue on ignition á281ñ: not more than 0.1%.
Chloroform-alcohol-insoluble substances— Warm 2g with 15mLof a mixture of chloroform and dehydrated alcohol (2:1)at about 50for 10minutes.Filter through a tared,sintered-glass filter,using gentle suction.Wash the filter with five 10-mLportions of the chloroform-alcohol mixture,dry at 105for 1hour,and weigh:the weight of the residue does not exceed 2mg (0.1%).
Limit of dihydroquinidine sulfate—
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 filtered and degassed mixture of water,acetonitrile,Methanesulfonic acid solution,and Diethylamine solution(860:100:20:20).Adjust with Diethylamine to a pHof 2.6.
System suitability solution— Transfer about 10mg each of quinidine sulfate and dihydroquinidine hydrochloride to a 50-mLvolumetric flask.Dissolve in about 5mLof methanol,dilute with Mobile phaseto volume,and mix.
Test solution— Transfer about 20mg of Quinidine Sulfate to a 100-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 235-nm detector and a 3.9-mm ×30-cm column that contains packing L1.Chromatograph the System suitability solution,and proceed as directed for Procedure:the relative retention times for quinidine and dihydroquinidine are 1and 1.5,respectively,the resolution,R,between the quinidine and dihydroquinidine is not less than 2.5,and the relative standard deviation for the peak response is not more than 2.0%.
Procedure— Inject about 50µLof the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.The response of the dihydroquinidine peak is not greater than 0.25that of the quinidine peak (20.0%).
Chromatographic purity—
Standard preparation— Prepare a solution of USP Quinidine Sulfate RSin diluted alcohol to contain 6mg per mL.
Diluted standard preparation— Dilute a portion of the Standard preparationwith diluted alcohol to a concentration of 0.06mg per mL.
Related substances preparation— Prepare a solution in diluted alcohol containing in each mL0.05mg of USP Quininone RS(corresponding to 0.06mg of the sulfate),and 0.10mg of cinchonine (corresponding to 0.12mg of the sulfate).
Test preparation— Prepare a solution of Quinidine Sulfate in diluted alcohol to contain 6mg per mL.
Procedure— Apply 10-µLportions of the Test preparation,the Standard preparation,the Diluted standard preparation,and the Related substances preparationto 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 preparationat the RFvalue of a spot produced by the Related substances preparationis not greater in size or intensity than that corresponding spot.Apart from these spots and from the spots appearing at the RFvalue of Quinidine Sulfate and dihydroquinidine sulfate (the two spots most evident from the Standard preparation),any additional fluorescent spot is not greater in size or intensity than the principal spot of the Diluted standard preparation.Spray the plate with potassium iodoplatinate TS.Any spot produced by the Test preparationis not greater in size or intensity than a corresponding spot from the Related substances preparation.
Organic volatile impurities,Method Iá467ñ: meets the requirements.
Assay— Dissolve about 200mg of Quinidine Sulfate,accurately weighed,in 20mLof acetic anhydride,and proceed as directed in the Assayunder Quinidine Gluconate,beginning with [add]“4drops of p-naphtholbenzein TS.”Each mLof 0.1Nperchloric acid is equivalent to 24.90mg of total alkaloid salt,calculated as (C20H24N2O2)2·H2SO4.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1694
Phone Number:1-301-816-8305