Norethindrone
;)
19-Norpregn-4-en-20-yn-3-one,17-hydroxy-,(17a)-.
17-Hydroxy-19-nor-17a-pregn-4-en-20-yn-3-one [68-22-4].
»Norethindrone contains not less than 97.0percent and not more than 102.0percent of C20H26O2,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Completeness of solution—
The solution called for in the test for Specific rotationis clear and free from undissolved solid.
Identification,Infrared Absorption á197Kñ.
Specific rotation á781Sñ:
between -30
and -38.
and -38.
Test solution:
20mg per mL,in dioxane.
Loss on drying á731ñ—
Dry it in vacuum at 105for 3hours:it loses not more than 0.5%of its weight.
for 3hours:it loses not more than 0.5%of its weight.
Limit of ethynyl group—
Dissolve 200mg in about 40mLof tetrahydrofuran.Add 10mLof silver nitrate solution (1in 10),and titrate with 0.1Nsodium hydroxide VS,either a glass-calomel or a silver–silver chloride electrode system with potassium nitrate filling solution.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nsodium hydroxide is equivalent to 2.503mg of ethynyl group (–CºCH).Not less than 8.18%and not more than 8.43%of ethynyl group is found.
Chromatographic purity—
Test solution—
Prepare a solution of Norethindrone in chloroform to contain 10mg per mL.
Standard solutions—
Prepare a solution of USP Norethindrone RSin chloroform to contain 10mg per mL(Standard stock solution).Dilute accurately measured volumes of Standard stock solutionwith chloroform to obtain Standard stock solutions A,B,C,and Dhaving known concentrations of 150,50,30,and 10µg per mL,respectively.
Procedure—
Separately apply 10µLof the Test solutionand 10µLof each Standard solutionto a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram in a solvent system consisting of a mixture of chloroform and methanol (95:5)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,mark the solvent front,and allow the solvent to evaporate.Spray the plate with a mixture of methanol and sulfuric acid (7:3),then heat the plate at 100for 5minutes:the RFvalue of the principal spot from the Test solutioncorresponds to that of the principal spot from Standard solution A.Compare the intensities of any secondary spots observed in the chromatogram of the Test solutionwith those of the principal spots in the chromatograms of the Standard solution:no secondary spot from the chromatogram of the Test solutionis larger or more intense than the principal spot obtained from Standard solution B(0.5%),and the sum of the intensities of the secondary spots obtained from the Test solutionis not more intense than the principal spot obtained from Standard solution A(1.5%).
for 5minutes:the RFvalue of the principal spot from the Test solutioncorresponds to that of the principal spot from Standard solution A.Compare the intensities of any secondary spots observed in the chromatogram of the Test solutionwith those of the principal spots in the chromatograms of the Standard solution:no secondary spot from the chromatogram of the Test solutionis larger or more intense than the principal spot obtained from Standard solution B(0.5%),and the sum of the intensities of the secondary spots obtained from the Test solutionis not more intense than the principal spot obtained from Standard solution A(1.5%).
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay—
Dissolve about 100mg of Norethindrone,accurately weighed,in alcohol,and dilute quantitatively and stepwise with alcohol to obtain a solution containing about 10µg per mL.Dissolve an accurately weighed quantity of USP Norethindrone RSin alcohol,and dilute quantitatively and stepwise with alcohol to obtain a Standard solution having a known concentration of about 10µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 240nm,using alcohol as the blank.Calculate the quantity,in mg,of C20H26O2in the portion of Norethindrone taken by the formula:
10C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Norethindrone RSin the Standard solution,and AUand ASare the absorbances of the solution of Norethindrone and the Standard solution,respectively.
Auxiliary Information—
Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1393
Phone Number:1-301-816-8139