Quinidine Gluconate Injection

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 Gluconate Injection is a sterile solution of Quinidine Gluconate in Water for Injection. Each mL contains amounts of quinidine gluconate and dihydroquinidine gluconate totaling to NLT 76 mg and NMT 84 mg of quinidine gluconate (C₂₀H₂₄N₂O₂ · C₆H₁₂O₇).

2 IDENTIFICATION

A.

Sample solution: 1-in-150 solution of Injection in dilute sulfuric acid (1 in 350)

Acceptance criteria: The Sample solution exhibits a vivid blue fluorescence. On the addition of a few drops of hydrochloric acid, the fluorescence disappears.

B.

Sample solution: 1-in-4 solution of Injection

Acceptance criteria: The Sample solution is dextrorotatory.

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

3 ASSAY

3.1 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: Dissolve 10.0 mL of diethylamine in water to prepare a 100-mL solution.

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

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

Standard solution: 0.26 mg/mL of USP Quinidine Gluconate RS in Mobile phase

Sample stock solution: Transfer a volume of Injection, equivalent to 400 mg of quinidine gluconate, to a 50-mL volumetric flask, and dilute with methanol to volume.

Sample solution: Transfer 3 mL of the Sample stock solution to a 100-mL volumetric flask, and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 3.9-mm × 30-cm column; 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 quantity in mg/mL of the sum of quinidine gluconate and dihydroquinidine gluconate in the portion of Injection taken:

Result =  (r_B,U + r_D,U)/(r_B,S + r_D,S) × (C_S/V) × F

r_B,U = 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 Gluconate RS in the Standard solution (mg/mL)

V = volume of the Injection taken (mL)

F = dilution factor, 5000/3

Acceptance criteria: Each mL contains amounts of quinidine gluconate and dihydroquinidine gluconate totaling to NLT 76 mg and NMT 84 mg of quinidine gluconate (C₂₀H₂₄N₂O₂ · C₆H₁₂O₇).

4 IMPURITIES

4.1 Organic Impurities

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

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

Standard solution C: 0.04 mg/mL of USP Quininone RS (corresponding to 0.06 mg of the gluconate) and 0.08 mg/mL of cinchonine (corresponding to 0.12 mg of the gluconate) in diluted alcohol

Sample solution: Mix, equivalent to 80 mg of quinidine gluconate from a volume of Injection, with 25 mL of water. Add 2 drops of 2 N sulfuric acid, and extract with 50 mL of ether, discarding the ether extract. To the aqueous solution add 2 mL of 1 N sodium hydroxide, extract with 50 mL of ether, wash the extract with 25 mL of water, and discard the aqueous solutions. Evaporate the ether extract just to dryness, and dissolve the residue in 10 mL of alcohol.

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 (5:4:1)

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 about 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 Rf 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 Rf value of quinidine gluconate and dihydroquinidine gluconate (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.

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: NMT 0.6 USP Endotoxin Unit/mg of quinidine gluconate

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or in multiple-dose containers, preferably of Type I glass.

USP Reference Standards 〈11〉

USP Quinidine Gluconate RS

USP Quininone RS

Cinchonan-9-one, 6′-methoxy-, (8α)-.

C₂₀H₂₂N₂O₂ 322.40