Clomiphene Citrate Tablets
»Clomiphene Citrate Tablets contain not less than 93.0percent and not more than 107.0percent of the labeled amount of C26H28ClNO·C6H8O7.
Packaging and storage—
Preserve in well-closed containers,protected from light.
Identification—
Place a portion of finely powdered Tablets,equivalent to about 30mg of clomiphene citrate,in a centrifuge tube containing about 30mLof a 1in 2solution of methanol in 0.1Nhydrochloric acid.Insert the stopper,and place the tube in a water bath at about 37
for 15minutes.Shake occasionally.Centrifuge,and place the clear supernatant in a separator.Extract with one 40-mLand two 25-mLportions of hexanes,and discard the extract.Render the aqueous solution alkaline with 1Nsodium hydroxide,and extract the precipitated base with one 50-mLand two 25-mLportions of hexanes.Wash the combined extracts with two portions of water.Dry the extract with anhydrous sodium sulfate,and remove the hexanes by evaporation under reduced pressure.Add about 1.0mLof carbon disulfide to the residue,and dissolve.Determine the absorption spectra of the test solution and of a Standard solution of USP Clomiphene Citrate RS,similarly prepared,as directed under Identification—Organic Nitrogenous Bases á181ñ.
for 15minutes.Shake occasionally.Centrifuge,and place the clear supernatant in a separator.Extract with one 40-mLand two 25-mLportions of hexanes,and discard the extract.Render the aqueous solution alkaline with 1Nsodium hydroxide,and extract the precipitated base with one 50-mLand two 25-mLportions of hexanes.Wash the combined extracts with two portions of water.Dry the extract with anhydrous sodium sulfate,and remove the hexanes by evaporation under reduced pressure.Add about 1.0mLof carbon disulfide to the residue,and dissolve.Determine the absorption spectra of the test solution and of a Standard solution of USP Clomiphene Citrate RS,similarly prepared,as directed under Identification—Organic Nitrogenous Bases á181ñ.
Dissolution á711ñ—
Medium:
water;900mL.
Apparatus 1:
100rpm.
Time:
30minutes.
Procedure—
Determine the amount of C26H28ClNO·C6H8O7dissolved from UVabsorbances at the wavelength of maximum absorbance at about 232nm of filtered portions of the solution under test,suitably diluted with 0.1Nhydrochloric acid,in comparison with a Standard solution having a known concentration of USP Clomiphene Citrate RSin the same medium.
Tolerances—
Not less than 75%(Q)of the labeled amount of C26H28ClNO·C6H8O7is dissolved in 30minutes.
Uniformity of dosage units á905ñ:
meet the requirements.
Assay—
Mobile phase,Standard preparation,System suitability solution,and Chromatographic system—
Proceed as directed in the Assay under Clomiphene Citrate.
Assay preparation—
Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 50mg of clomiphene citrate,to a 100-mLvolumetric flask.Add about 50mLof Mobile phase,and stir using a magnetic bar for about 30minutes.Remove the magnetic bar from the flask,dilute with Mobile phaseto volume,mix,and filter.Transfer 10.0mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,mix,and filter,discarding the first 10mL.[NOTE—This solution is stable for at least 24hours.]
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 C26H28ClNO·C6H8O7in the portion of Tablets taken by the formula:
1000C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Clomiphene Citrate RSin the Standard preparation,and rUand rSare the peak responses 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 508
Phone Number:1-301-816-8139