(kwin' i deen sul' fate).
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 Cinchona and their hybrids and from Remijia pedunculata Flückiger (Fam. Rubiaceae), or prepared from quinine. It contains not less than 99.0 percent and not more than 101.0 percent of total alkaloid salt, calculated as (C20H24N2O2)2·H2SO4, on the anhydrous basis.
Packaging and storage Preserve in well-closed, light-resistant containers.
USP Reference standards 11
A: A 1 in 2000 solution in dilute sulfuric acid (1 in 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 RF value of the principal spot obtained from the Test preparation corresponds to that from the Standard preparation.
C: A 1 in 50 solution made with the aid of a few drops of hydrochloric acid responds to the tests for Sulfate 191.
Specific rotation 781: between +275 and +288, calculated on the anhydrous basis, determined in a solution in 0.1 N hydrochloric acid containing 200 mg in each 10 mL.
Water, Method I 921: between 4.0% and 5.5%.
Residue on ignition 281: not more than 0.1%.
Chloroform-alcohol-insoluble substances Warm 2 g with 15 mL of a mixture of chloroform and dehydrated alcohol (2:1) at about 50 for 10 minutes. Filter through a tared, sintered-glass filter, using gentle suction. Wash the filter with five 10-mL portions of the chloroform-alcohol mixture, dry at 105 for 1 hour, and weigh: the weight of the residue does not exceed 2 mg (0.1%).
Heavy metals, Method II 231: 0.001%.
Limit of dihydroquinidine sulfate
Methanesulfonic acid solution Add 35.0 mL of methanesulfonic acid to 20.0 mL of glacial acetic acid, dilute with water to 500 mL, and mix.
Diethylamine solution Dissolve 10.0 mL of diethylamine in water to obtain 100 mL of 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 pH of 2.6.
System suitability solution Transfer about 10 mg each of quinidine sulfate and dihydroquinidine hydrochloride to a 50-mL volumetric flask. Dissolve in about 5 mL of methanol, dilute with Mobile phase to volume, and mix.
Test solution Transfer about 20 mg of Quinidine Sulfate to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)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 1 and 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 50 µL of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. The response of the dihydroquinidine peak is not greater than 0.25 that of the quinidine peak (20.0%).
Standard preparation Prepare a solution of USP Quinidine Sulfate RS in diluted alcohol to contain 6 mg per mL.
Diluted standard preparation Dilute a portion of the Standard preparation with diluted alcohol to a concentration of 0.06 mg per mL.
Related substances preparation Prepare a solution in diluted alcohol containing in each mL 0.05 mg of USP Quininone RS (corresponding to 0.06 mg of the sulfate), and 0.10 mg of cinchonine (corresponding to 0.12 mg of the sulfate).
Test preparation Prepare a solution of Quinidine Sulfate in diluted alcohol to contain 6 mg per mL.
Procedure Apply 10-µL portions of the Test preparation, the Standard preparation, the Diluted standard preparation, and the Related substances preparation to a suitable thin-layer chromatographic plate (see Chromatography 621) 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 15 cm, 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 UV light. Any spot produced by the Test preparation at the RF value of a spot produced by the Related substances preparation is not greater in size or intensity than that corresponding spot. Apart from these spots and from the spots appearing at the RF value 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 preparation is not greater in size or intensity than a corresponding spot from the Related substances preparation.
Assay Dissolve about 200 mg of Quinidine Sulfate, accurately weighed, in 20 mL of acetic anhydride, and proceed as directed in the Assay under Quinidine Gluconate, beginning with [add] 4 drops of p-naphtholbenzein TS. Each mL of 0.1 N perchloric acid is equivalent to 24.90 mg of total alkaloid salt, calculated as (C20H24N2O2)2 · H2SO4.
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USP35NF30 Page 4505