Digoxin Oral Solution
» Digoxin Oral Solution contains, in each 100 mL, not less than 4.50 mg and not more than 5.25 mg of digoxin (C41H64O14).
Packaging and storage Preserve in tight containers, and avoid exposure to excessive heat.
USP Reference standards 11
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 Ttrichloroacetic acid reagentMix 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 Proceed as directed for Procedure in the test for Related glycosides under Digoxin, except to omit the use of the Gitoxin standard solution. Examine the plate under long-wavelength UV light: the RF value of the principal spot in the chromatogram of the Test solution corresponds to that in the chromatogram of the Standard solution.
Alcohol content 611: between 90.0% and 115.0% of the labeled amount of C2H5OH.
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 × 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(rU / rS)in which C is the concentration, in µg per mL, of USP Digoxin RS in the Standard preparation; and rU and rS are the digoxin peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2906Pharmacopeial Forum: Volume No. 31(5) Page 1361