(Official April 1, 2006)

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

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

C: In the test for Chromatographic purity, the RF value of the principal spot obtained from the Test solution corresponds to that obtained from the Standard solution.

TEST 1— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 1.

TEST 4— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 4.

TEST 5— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 5.

TEST 1— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1.

TEST 4— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

TEST 5— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.

(Official April 1, 2006)

Procedure for content uniformity— Quantitatively transfer 1 intact or powdered Tablet to a 250-mL volumetric flask, and add about 125 mL of 0.1 N hydrochloric acid. Heat the sample with frequent agitation just to boiling, and cool to room temperature. Dilute with 0.1 N hydrochloric acid to volume, mix, and filter, discarding the first 20 mL of the filtrate. Concomitantly determine the absorbance of this solution, quantitatively diluted with 0.1 N hydrochloric acid, if necessary, and a Standard solution of USP Quinidine Gluconate RS in 0.1 N hydrochloric acid having a known concentration of about 0.0525 mg per mL, in 1-cm cells, at the wavelength of maximum absorbance at about 347 nm, with a suitable spectrophotometer, using 0.1 N hydrochloric 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 T is the labeled quantity, in mg, of quinidine gluconate in the Tablet; D is 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; C is the concentration, in mg per mL, of USP Quinidine Gluconate RS in the Standard solution; and AU and AS are the absorbances of the solution from the Tablet and the Standard solution, respectively.

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

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

Quininone solution— Prepare a solution in diluted alcohol containing in each mL 0.04 mg of USP Quininone RS (corresponding to 0.06 mg of the gluconate).

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

Procedure— Apply 10-µL portions of the Test solution, the Standard solution, the Diluted standard solution, and the Quininone solution 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 solution at the RF value of a spot produced by the Quininone solution 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 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 obtained from the Diluted standard solution.

(Official January 1, 2007)

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

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

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

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 160 mg of quinidine gluconate, to a 100-mL volumetric flask, add about 80 mL of 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 20 mL of the filtrate. Transfer 3.0 mL of the filtrate to a 25-mL volumetric flask, 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- to 5-mm × 25- to 30-cm column that contains packing L1. The flow rate is about 1.5 mL per 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 1 and 1.5, respectively; and the resolution, R, between quinidine and dihydroquinidine 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 20 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Quinidine Gluconate RS in the Standard preparation; rb,U and rb,S are the peak responses of quinidine obtained from the Assay preparation and the Standard preparation, respectively; and rd,U and rd,S are the peak responses of dihydroquinidine obtained from the Assay preparation and the Standard preparation, respectively.