Digoxin Oral Solution

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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» Digoxin Oral Solution contains, in each 100 mL, not less than 4.50 mg and not more than 5.25 mg of digoxin (C₄₁H₆₄O₁₄).

1 Packaging and storage-

Preserve in tight containers, and avoid exposure to excessive heat.

2 USP REFERENCE STANDARDS (11)-

USP Digoxin RS

3 Identification-

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

B: Chloramine T-trichloroacetic acid reagent-Mix 10 mL of a freshly prepared solution of chloramine T (3 in 100) and 40 mL of a 1 in 4 solution of trichloroacetic acid in dehydrated alcohol.

Spotting solvent-Prepare a mixture of chloroform and methanol (2:1).

Standard solution-Dissolve an accurately weighed quantity of USP Digoxin RS in Spotting solvent to obtain a solution containing 0.25 mg per mL.

Test solution-Pipet a volume of Oral Solution, equivalent to 0.5 mg of digoxin, into a separator. Add sufficient water to obtain a final volume of approximately 50 mL. Extract the aqueous layer with three 30-mL portions of chloroform, combining the extracts in a conical flask. Evaporate the combined chloroform extracts on a steam bath with the aid of a current of air to dryness. Add 2 mL of Spotting solvent to the residue, and shake for 2 minutes.

Procedure-Apply 10 µL of the Test solution and 10 µL of the Standard solution on a line parallel to and about 2.5 cm from the bottom edge of a reversed-phase thin-layer chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel mixture to which is permanently bonded octadecylsilane (C18). Allow the spots to dry, and place the plates in a developing chamber containing a mixture of methanol and water (7:3). Develop the chromatogram until the solvent front has moved about 15 cm above the line of application. Remove the plate, and allow the solvent to evaporate. Spray the plate with Chloramine T-trichloroacetic acid reagent, freshly mixed, and heat in an oven at 110° for 10 minutes. Examine the plate under long-wavelength UV light: the R_F value of the principal spot in the chromatogram of the

Test solution corresponds to that in the chromatogram of the Standard solution.

ALCOHOL DETERMINATION (611): between 90.0% and 115.0% of the labeled amount of C₂H₅OH.

4 Assay-

Mobile phase-Prepare a filtered and degassed mixture of water, acetonitrile, and isopropyl alcohol (70:27.5:2.5). Make adjustments if necessary (see System Suitability under Chromatography (621)).

Standard preparation-Dissolve an accurately weighed quantity of USP Digoxin RS in diluted alcohol, and dilute quantitatively and stepwise with diluted alcohol to obtain a solution having a known concentration of about 20 µg per mL.

Assay preparation-Transfer an accurately measured volume of 10.0 mL of Oral Solution, equivalent to about 500 µg of digoxin, to a 25-mL volumetric flask, dilute with diluted alcohol to volume, and mix.

System suitability preparation-Prepare as directed in the Assay under Digoxin.

Chromatographic system (see CHROMATOGRAPHY (621)) -The liquid chromatograph is equipped with a 218-nm detector and a 4.6-mm x 15-cm column that contains packing L1. The flow rate is about 0.5 mL per minute. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the resolution, R, between digoxin and digoxigenin bisdigitoxoside is not less than 2.0; the tailing factor for the analyte peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure-Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in µg, of digoxin (C₄₁H₆₄O₁₄) in each mL of the Oral Solution taken by the formula:

                2.5C(r_U/r_S)

in which C is the concentration, in µg per mL, of USP Digoxin RS in the Standard preparation; and r_U and r_S are the digoxin peak responses obtained from the Assay preparation and the Standard preparation, respectively.