Ethynodiol Diacetate and Ethinyl Estradiol Tablets
»Ethynodiol Diacetate and Ethinyl Estradiol Tablets contain not less than 93.0percent and not more than 107.0percent of the labeled amount of ethynodiol diacetate (C24H32O4),and not less than 90.0percent and not more than 110.0percent of the labeled amount of ethinyl estradiol (C20H24O2).
Packaging and storage— Preserve in well-closed containers.
Identification— Place a quantity of finely powdered Tablets,equivalent to about 10mg of ethynodiol diacetate,in a stoppered 15-mLcentrifuge tube.Add 10mLof acetonitrile,insert the stopper in the tube,and mix by shaking and inversion for about 2minutes.Centrifuge at about 1200rpm for 10minutes,and decant the supernatant through filter paper into a suitable container.Evaporate a 5-mLaliquot of the filtrate on a steam bath with the aid of a stream of nitrogen,and dissolve the residue in 1mLof chloroform.Apply 20µLeach of the solution under test,a Standard solution of USP Ethynodiol Diacetate RSin chloroform containing 5mg per mL,and a Standard solution of USP Ethinyl Estradiol RSin chloroform containing 0.25mg per mLat points about 3cm from one end of a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Place the plate in a developing chamber containing a mixture of 3volumes of ethyl acetate and 7volumes of cyclohexane to a depth of 2cm,the developing chamber previously having been equilibrated with the solvent mixture as described under Thin-Layer Chromatographyunder Chromatography á621ñ.Remove the plate when the solvent moves to about 15cm above the initial spots,allow it to dry in air at room temperature,spray it with a 1in 10solution of phosphomolybdic acid in alcohol,and heat it at 80for 10minutes:the spots from the solution under test and the Standard solutions appear dark on a light-green background.The ethynodiol diacetate and ethinyl estradiol spots from the solution under test have the same relative positions on the plate as the spots from the Standard solutions.The RFvalues of ethynodiol diacetate and of ethinyl estradiol in this system are about 0.8and about 0.4,respectively.
Disintegration á701ñ: 15minutes,the use of disks being omitted.
Uniformity of dosage units á905ñ: meet the requirements for Content Uniformitywith respect to ethynodiol diacetate and to ethinyl estradiol.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of methanol,acetonitrile,and water (15:35:50).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve,with the aid of sonication if necessary,accurately weighed quantities of USP Ethynodiol Diacetate RSand USP Ethinyl Estradiol RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having known concentrations,in mg per mL,of the Reference Standards,corresponding to about one-twenty-fifth of the labeled amounts of ethynodiol diacetate and ethinyl estradiol in the Tablets.
Assay preparation— Place 10Tablets in a 250-mLvolumetric flask.Add a portion of Mobile phase,and sonicate until the Tablets are completely disintegrated.Cool to room temperature,dilute with Mobile phaseto volume,mix,and filter.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm ×25-cm column that contains packing L10.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the tailing factor is not more than 1.5,and the column efficiency is not less than 3000theoretical plates,both based on the ethynodiol diacetate peak,and the relative standard deviation for replicate injections is not more than 2.0%for each peak due to ethynodiol diacetate and ethinyl estradiol.
Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of ethynodiol diacetate (C24H32O4)and ethinyl estradiol (C20H24O2)in each Tablet taken by the formula:
25C(rU/rS),
in which Cis the concentration,in mg per mL,of the appropriate Reference Standard in the Standard preparation,and rUand rSare the peak responses,at the corresponding retention times,obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 797
Phone Number:1-301-816-8139
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