Quinidine Sulfate Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Quinidine Sulfate Tablets contain amounts of quinidine sulfate and dihydroquinidine sulfate totaling NLT 90.0% and NMT 110.0% of the labeled amount of quinidine sulfate, calculated as quinidine sulfate [(C₂₀H₂₄N₂O₂)₂ · H₂SO₄ · 2H₂O].

2 IDENTIFICATION

3 A.

Analysis: Shake the equivalent to 100 mg of quinidine sulfate from powdered Tablets, with 10 mL of dilute sulfuric acid (1 in 350), and filter.

Acceptance criteria: An appropriate dilution of the filtrate exhibits a vivid blue fluorescence. On the addition of a few drops of hydrochloric acid, the fluorescence disappears.

3.1 B.

The R value of the principal spot of the Sample solution corresponds to that of the Standard solution, as obtained in Organic Impurities.

3.2 C. Identification Tests—General, Sulfate 〈191〉

Analysis: Shake the equivalent to 100 mg of quinidine sulfate from powdered Tablets, with 10 mL of dilute hydrochloric acid (1 in 100), and filter.

Acceptance criteria: The filtrate meets the requirements.

4 ASSAY

4.1 Procedure

Solution A: Add 35.0 mL of methanesulfonic acid to 20.0 mL of glacial acetic acid, and dilute with water to 500 mL.

Solution B: Dilute 10.0 mL of diethylamine with water to 100 mL.

Mobile phase: Acetonitrile, Solution B, Solution A, and water (100:20:20:860). Adjust with diethylamine to a pH of 2.6.

System suitability solution: 0.2 mg/mL each of USP Quinidine Sulfate RS and dihydroquinidine hydrochloride prepared as follows. Dissolve a suitable quantity of each USP Quinidine Sulfate RS and dihydroquinidine hydrochloride in about 10% of total volume of methanol, and dilute with Mobile phase to volume.

Standard solution: 0.2 mg/mL of USP Quinidine Sulfate RS in Mobile phase

Sample stock solution: Weigh and finely powder NLT 20 Tablets. Transfer a portion of the powder, nominally equivalent to 160 mg of quinidine sulfate, to a 100-mL volumetric flask. Add 80 mL of methanol, and shake the flask by mechanical means for 30 min. Dilute with methanol to volume, and filter, discarding the first 10 mL of filtrate.

Sample solution: Nominally equivalent to 0.192 mg/mL of quinidine sulfate in Mobile phase from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 3.9-mm × 30-cm; packing L1

Injection volume: 50 µL

System suitability

Sample: System suitability solution

[Note—The relative retention times for quinidine and dihydroquinidine are 1 and 1.5, respectively.]

Suitability requirements

Resolution: NLT 2.5 between quinidine and dihydroquinidine

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of quinidine sulfate (quinidine sulfate and dihydroquinidine sulfate) in the portion of the Tablets taken:

Result = [(r_B,D + r_D,U)/(r_B,S + r_D,S)] × (C_S/C_U) × 100

r_B,D = peak response of quinidine from the Sample solution

r_D,U = peak response of dihydroquinidine from the Sample solution

r_B,S = peak response of quinidine from the Standard solution

r_D,S = peak response of dihydroquinidine from the Standard solution

C_S = concentration of USP Quinidine Sulfate RS in the Standard solution (mg/mL)

C_U = nominal concentration of quinidine sulfate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

5 PERFORMANCE TESTS

5.1 Dissolution 〈711〉

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: USP Quinidine Sulfate RS in Medium

Sample solution: Dilute with Medium to a concentration that is similar to the Standard solution. Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

Mode: UV

Analytical wavelength: 248 nm

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 85% (Q) of the labeled amount of quinidine sulfate [(C₂₀H₂₄N₂O₂)₂ · H₂SO₄ · 2H₂O] is dissolved.

Change to read:

5.2 Uniformity of Dosage Units 〈905〉: Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Standard solution: 40 µg/mL of USP Quinidine Sulfate RS in dilute hydrochloric acid (1 in 100)

Sample solution: Transfer a crushed Tablet to a 250-mL volumetric flask, add 175 mL of dilute hydrochloric acid (1 in 100), and shake by mechanical means for 30 min. Add dilute hydrochloric acid (1 in 100) to volume. Filter a portion of the mixture, discarding the first 20 mL of the filtrate. Dilute quantitatively, if necessary.

Instrumental conditions

Mode: UV

Cell: 1 cm

Analytical wavelength: 345 nm

Blank: Water

Analysis

Samples: Standard solution, Sample solution, and Blank

Calculate the percentage of the labeled amount of quinidine sulfate and dihydroquinidine sulfate, calculated as quinidine sulfate [(C₂₀H₂₄N₂O₂)₂ · H₂SO₄ · 2H₂O], in the Tablet taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Quinidine Sulfate RS in the Standard solution (mg/mL)

C_U = nominal concentration of quinidine sulfate in the Sample solution (mg/mL)

(CN 1-Aug-2023)

6 IMPURITIES

6.1 Organic Impurities

Standard solution A: 6 mg/mL of USP Quinidine Sulfate RS in diluted alcohol

Standard solution B: 0.06 mg/mL of USP Quinidine Sulfate RS in diluted alcohol from Standard solution A

Standard solution C: 0.05 mg/mL of USP Quininone RS (corresponding to 0.06 mg of the sulfate) and 0.10 mg/mL of cinchonine (corresponding to 0.12 mg of the sulfate) in diluted alcohol

Sample solution: Equivalent to 6 mg/mL of quinidine sulfate in diluted alcohol prepared as follows. Shake an amount equivalent to 150 mg of quinidine sulfate from a suitable amount of powdered Tablets in 25 mL of diluted alcohol for 10 min, and filter.

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Developing solvent system: Chloroform, acetone, and diethylamine (50:40:10)

Analysis

Samples: Standard solution A, Standard solution B, Standard solution C, and Sample solution

Proceed as directed in the chapter. The solvent chamber is used without previous equilibration. When the solvent front has moved 15 cm, remove the plate from the chamber, mark the solvent front, and allow the solvent to evaporate. Spray with glacial acetic acid. Locate the spots on the plate by examination under long-wavelength UV light. Then spray the plate with potassium iodoplatinate TS.

Acceptance criteria: Any spot produced by the Sample solution at the R value of a spot produced by Standard solution C is not greater in size or intensity than that corresponding spot. Apart from these spots and from the spots appearing at the R value of quinidine sulfate and dihydroquinidine sulfate (the two spots most evident from Standard solution A), any additional fluorescent spot is not greater in size or intensity than the principal spot of Standard solution B. After the treatment with potassium iodoplatinate TS, any spot produced by the Sample solution is not greater in size or intensity than a corresponding spot from Standard solution C.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.

USP Reference Standards 〈11〉

USP Quinidine Sulfate RS

USP Quininone RS

Cinchonan-9-one, 6′-methoxy-, (8alpha)-

C₂₀H₂₂N₂O₂ 322.40