Estradiol Tablets
»Estradiol Tablets contain not less than 90.0percent and not more than 115.0percent of the labeled amount of C18H24O2.
Packaging and storage— Preserve in tight,light-resistant containers.
Identification— Place a quantity of finely powdered Tablets,equivalent to about 4mg of estradiol,in a screw-capped,20-mLvial.Add 10mLof chloroform,and sonicate for 2minutes.Filter through medium-porosity filter paper.Apply 20µLeach of this solution and a Standard solution of USP Estradiol RSin chloroform containing 0.4mg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a lined chamber with a solvent system consisting of a mixture of toluene and acetone (4:1)until the solvent front has moved 10cm beyond the starting line.Remove the plate from the developing chamber,mark the solvent front,and allow to air-dry.Spray the plate with a mixture of methanol and sulfuric acid (1:1),and heat at 100for about 5minutes:the principal spots obtained from the test solution and the Standard solution have the same color and RFvalue.
Dissolution á711ñ—
Medium: 0.3%sodium lauryl sulfate in water;500mL.
Apparatus 2: 100rpm.
Time: 60minutes.
Mobile phase— Prepare a suitable degassed and filtered solution of water and acetonitrile (55:45).
Standard solution— Prepare a solution of USP Estradiol RSin methanol having an accurately known concentration of about 0.02mg per mL.Dilute aliquots of this solution with Mediumto obtain a final solution having a concentration approximately equal to the expected concentration of drug in the Medium,assuming 100%dissolution.
Test solution— Use a filtered portion of the solution under test from the dissolution vessel.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 205-nm detector and a 4.6-mm ×7.5-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph replicate injections of the Standard preparation,and record the peak areas as directed for Procedure:the tailing factor is not more than 2.0;and the relative standard deviation is not more than 2.0%.
Procedure— Separately inject equal volumes (about 100µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity of C18H24O2dissolved by comparison of the peak areas obtained from the Test solutionand the Standard solution.
Tolerances— Not less than 75%(Q)of the labeled amount of C18H24O2is dissolved in 60minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
Mobile phase,Internal standard solution,Standard preparation,andChromatographic system— Proceed as directed in the Assayunder Estradiol.
Assay preparation— Weigh and finely powder not fewer than 10Tablets.Transfer a portion of the powder,equivalent to about 8mg of estradiol,to a 100-mLvolumetric flask.Add 4mLof water,and swirl.Add 10.0mLof Internal standard solutionand about 60mLof methanol.Shake by mechanical means for 15minutes,dilute with methanol to volume,mix,and allow the solids to settle.Filter a portion,discarding the first 10mLof the filtrate.Mix 5.0mLof the subsequent filtrate with 5.0mLof methanol and 10.0mLof water.
Procedure— Proceed as directed for Procedurein the Assayunder Estradiol.Calculate the quantity,in mg,of C18H24O2in the portion of Tablets taken by the formula:
0.4C(RU/RS),
in which the terms are as defined therein.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 774
Phone Number:1-301-816-8139