Estradiol and Norethisterone Tablets
Action and use
Estrogen.
Definition
Estradiol and Norethisterone Tablets contain Estradiol Hemihydrate and Norethisterone. They are coated.
Content of estradiol, C18H24O2
95.0 to 105.0% of the stated amount.
Content of norethisterone, C20H26O2
95.0 to 105.0% of the stated amount.
Identification
10 volumes of acetone and 90 volumes of dichloromethane.
The chromatogram obtained with solution (1) shows two clearly separated spots with Rf values corresponding to those observed in the chromatogram obtained with solution (2).
Tests
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
450 volumes of water and 550 volumes of acetonitrile.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between each pair of peaks (estradiol and norethisterone, and estrone and norethisterone acetate) is at least 1.0.
Calculate the total content of estradiol, C18H24O2, and norethisterone, C20H26O2, in the medium from the chromatograms obtained and using the declared content of C18H24O2 in estradiol hemihydrate BPCRS and C20H26O2 in norethisterone BPCRS.
Estrone
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Dissolution may be used, but using an injection volume of 20 µL.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between each pair of peaks (estradiol and norethisterone, and estrone and norethisterone acetate) is at least 1.0.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to estrone is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Uniformity of content
Tablets containing less than the equivalent of 2 mg and/or less than 2% w/w of estradiol comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Dissolution may be used, but using an injection volume of 20 µL.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between each pair of peaks (estradiol and norethisterone, and estrone and norethisterone acetate) is at least 1.0.
Calculate the content of C18H24O2 and C20H26O2 in each tablet using the declared content of C18H24O2 in estradiol hemihydrate BPCRS and the declared content of C20H26O2 in norethisterone BPCRS.
Assay
For estradiol
For tablets containing the equivalent of less than 2 mg and/or less than 2% w/w of estradiol
Use the average of the individual results determined in the test for Uniformity of content.
For tablets containing the equivalent of 2 mg or more and 2% w/w or more of estradiol
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Dissolution may be used, but using an injection volume of 20 µL.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between each pair of peaks (estradiol and norethisterone, and estrone and norethisterone acetate) is at least 1.0.
Calculate the total content of estradiol, C18H24O2, in the tablets using the declared content of C18H24O2 in estradiol hemihydrate BPCRS.
For norethisterone
Use the average of the individual results determined in the test for Uniformity of content.
Storage
Estradiol and Norethisterone Tablets should be protected from light.
Labelling
The quantity of Estradiol Hemihydrate is stated in terms of the equivalent amount of estradiol.
Impurities
The impurities limited by the requirements of this monograph include: