Digoxin Elixir
(Current title—not to change until June 1,2005)
Monograph title change—to become official June 1,2005
See Digoxin Oral Solution
»Digoxin Elixir contains,in each 100mL,not less than 4.50mg and not more than 5.25mg of C41H64O14.
Packaging and storage— Preserve in tight containers,and avoid exposure to excessive heat.
Identification—
A: The retention time of the major peak in the chromatogram of Elixir corresponds to that of the Standard preparation,as obtained in the Assay.
B: Chloramine T–trichloroacetic acid reagent—Mix 10mLof a freshly prepared solution of chloramine T(3in 100)and 40mLof a 1in 4solution 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 RSin Spotting solventto obtain a solution containing 0.25mg per mL.
Test solution— Pipet a volume of Elixir,equivalent to 0.5mg of digoxin,into a separator.Add sufficient water to obtain a final volume of approximately 50mL.Extract the aqueous layer with three 30-mLportions 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 2mLof Spotting solventto the residue,and shake for 2minutes.
Procedure— Proceed as directed for Procedurein the test for Related glycosidesunder Digoxin,except to omit the use of the Gitoxin standard solution.Examine the plate under long-wavelength UVlight:the RFvalue of the principal spot in the chromatogram of the Test solutioncorresponds to that of the Standard solution.
Alcohol content á611ñ: between 90.0%and 115.0%of the labeled amount of C2H5OH.
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 Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Digoxin RSin diluted alcohol,and dilute quantitatively and stepwise with diluted alcohol to obtain a solution having a known concentration of about 20µg per mL.
Assay preparation— Transfer an accurately measured volume of Elixir,equivalent to about 500µg of digoxin,to a 25-mLvolumetric flask,dilute with diluted alcohol to volume,and mix.
System suitability preparation— Prepare as directed in the Assayunder Digoxin.
Chromatographic system (see Chromatography á621ñ)— 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 0.5mLper minute.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the tailing factor for the analyte peak is not more than 2.0;the resolution,R,between the digoxin and digoxigenin bisdigitoxoside peaks is not less than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in µg,of C41H64O14in each mLof the Elixir taken by the formula:
(100C/V)(rU/rS),
in which Cis the concentration,in µg per mL,of USP Digoxin RSin the Standard preparation;Vis the volume,in mL,of Elixir taken;and rUand rSare the digoxin peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Gabriel I.Giancaspro,Ph.D.,Senior Scientist and Latin American Specialist
Expert Committee:(DSB)Dietary Supplements:Botanicals
USP28–NF23Page 646
Pharmacopeial Forum:Volume No.28(2)Page 279
Phone Number:1-301-816-8343