Desogestrel and Ethinyl Estradiol Tablets
» Desogestrel and Ethinyl Estradiol Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of desogestrel (C22H30O) and ethinyl estradiol (C20H24O2).
Packaging and storage—
Preserve in well-closed containers.
Labeling—
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
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Identification—
A:
Thin-Layer Chromatographic Identification Test 
201
—
201—
Test solution—
Transfer a number of Tablets, equivalent to 1.5 mg desogestrel and 0.3 mg ethinyl estradiol, to a suitable container, add 50 mL of water, and sonicate until the Tablets disintegrate (if necessary, remove any coating with water before sonication). Place the sample in a separatory funnel, add 25 mL of ether, and shake well to extract the actives. Using a glass pipet, transfer the ether layer to a clean beaker, and evaporate to about 10 mL.
Standard solution—
Dissolve a quantity of USP Desogestrel RS and USP Ethinyl Estradiol RS in ether to obtain a solution containing about 0.15 mg per mL and 0.03 mg per mL, respectively.
Application volume:
30 µL.
Developing solvent system:
a mixture of chloroform and alcohol (96:4).
Procedure—
Proceed as directed in the chapter, and then air-dry. Spray the plate with a mixture of methanol and sulfuric acid (50:50), place in an oven at 105
for about 5 minutes, and examine the plate: meets the requirements.
for about 5 minutes, and examine the plate: meets the requirements.
B:
The retention times of the major peaks in the chromatogram of the Assay preparation corresponds to those in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711—
711—
test 1—
Medium:
0.05% sodium lauryl sulfate with an assay content of not less than 95%; 500 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Determine the amounts of desogestrel (C22H30O) and ethinyl estradiol (C20H24O2) dissolved by employing the following method.
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile and 20 mM potassium phosphate buffer, pH 6.0 (50:50). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Desogestrel standard stock solution—
Dissolve an accurately weighed quantity of USP Desogestrel RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 0.25 mg per mL.
Ethinyl estradiol standard stock solution—
Dissolve an accurately weighed quantity of USP Ethinyl Estradiol RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 0.25 mg per mL.
Desogestrel diluted standard solution—
Transfer 1.0 mL of Desogestrel standard stock solution to a 50-mL volumetric flask. Dilute with Medium to volume, and mix. This solution contains about 0.005 mg per mL of USP Desogestrel RS.
Ethinyl estradiol diluted standard solution—
Transfer 1.0 mL of Ethinyl estradiol standard stock solution to a 50-mL volumetric flask. Dilute with Medium to volume, and mix. This solution contains about 0.005 mg per mL of USP Ethinyl Estradiol RS.
Standard solution—
Dilute quantitative portions of Desogestrel diluted standard solution and Ethinyl estradiol diluted standard solution with Medium to obtain a solution containing about 0.3 µg per mL and 0.06 µg per mL of USP Desogestrel RS and USP Ethinyl Estradiol RS, respectively.
Test solution—
Centrifuge a portion of the dissolution sample, and use the clear supernatant.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 210-nm detector (for desogestrel analysis); a spectrofluorometric detector (for ethinyl estradiol analysis) with an excitation wavelength of 285 nm and an emission wavelength of 310 nm; a 4.6-mm × 15-cm column that contains packing L11; and a 4.6-mm × 12.5-mm guard column that also contains packing L11. The flow rate is about 2 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.2 for ethinyl estradiol and 1.0 for desogestrel, and the relative standard deviation is not more than 3.0%.
621)—
The liquid chromatograph is equipped with a 210-nm detector (for desogestrel analysis); a spectrofluorometric detector (for ethinyl estradiol analysis) with an excitation wavelength of 285 nm and an emission wavelength of 310 nm; a 4.6-mm × 15-cm column that contains packing L11; and a 4.6-mm × 12.5-mm guard column that also contains packing L11. The flow rate is about 2 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.2 for ethinyl estradiol and 1.0 for desogestrel, and the relative standard deviation is not more than 3.0%.
Procedure—
Separately inject equal volumes (about 200 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of C22H30O and C20H24O2 dissolved by the formula:
(0.5C)(100/K)(rU / rS)
in which C is the concentration, in µg per mL, of USP Desogestrel RS or USP Ethinyl Estradiol RS in the Standard solution; K is the labeled amount, in mg per Tablet, of C22H30O or C20H24O2; and rU and rS are the peak responses for desogestrel or ethinyl estradiol obtained from the Test solution and the Standard solution, respectively.
Tolerances—
Not less than 80% (Q) of each of the labeled amounts of C22H30O and C20H24O2 is dissolved in 30 minutes.
test 2—
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
0.3% sodium lauryl sulfate; 500 mL.
Apparatus 2:
100 rpm.
Time:
30 minutes.
Determine the amounts of desogestrel (C22H30O) and ethinyl estradiol (C20H24O2) dissolved by the chromatographic method used in Test 1.
Tolerances—
Not less than 80% (Q) of each of the labeled amounts of C22H30O and C20H24O2 is dissolved in 30 minutes.
Uniformity of dosage units 905:
meet the requirements for Content Uniformity with respect to desogestrel and to ethinyl estradiol.
905:
meet the requirements for Content Uniformity with respect to desogestrel and to ethinyl estradiol.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile and 20 mM potassium phosphate buffer, pH 6.0 (50:50). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Diluent—
Prepare a mixture of acetonitrile and water (50:50).
Desogestrel standard stock solution—
Dissolve an accurately weighed quantity of USP Desogestrel RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 0.3 mg per mL.
Ethinyl estradiol standard stock solution—
Dissolve an accurately weighed quantity of USP Ethinyl Estradiol RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 0.3 mg per mL.
Standard preparation—
Dilute appropriate aliquots of Desogestrel standard stock solution and Ethinyl estradiol standard stock solution with Diluent to obtain a solution having a known concentration of about 0.6 µg per mL and 0.12 µg per mL of USP Desogestrel RS and USP Ethinyl Estradiol RS, respectively.
Assay preparation—
Transfer 20 Tablets into a 200-mL volumetric flask. Add about 120 mL of Diluent, and shake for about 30 minutes. Dilute with Diluent to volume, and mix. Centrifuge a portion of the sample, and transfer an accurately measured volume to a 50-mL volumetric flask to obtain a final concentration of about 0.6 µg per mL of desogestrel. Dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 210-nm detector (for desogestrel analysis); a spectrofluorometric detector (for ethinyl estradiol analysis) with an excitation wavelength of 285 nm and an emission wavelength of 310 nm; a 4.6-mm × 15-cm column that contains packing L11; and a 4.6-mm × 12.5-mm guard column that also contains packing L11. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.2 for ethinyl estradiol and 1.0 for desogestrel; the tailing factor for both analytes is not more than 2.0; and the relative standard deviation is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 210-nm detector (for desogestrel analysis); a spectrofluorometric detector (for ethinyl estradiol analysis) with an excitation wavelength of 285 nm and an emission wavelength of 310 nm; a 4.6-mm × 15-cm column that contains packing L11; and a 4.6-mm × 12.5-mm guard column that also contains packing L11. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.2 for ethinyl estradiol and 1.0 for desogestrel; the tailing factor for both analytes is not more than 2.0; and the relative standard deviation is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 200 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of desogestrel (C22H30O) and ethinyl estradiol (C20H24O2) in the portion of Tablets taken by the formula:
100(CS/CU)(rU / rS)
in which CS is the concentration, in mg per mL, of USP Desogestrel RS or USP Ethinyl Estradiol RS in the Standard preparation;CU is the concentration, in mg per mL, of desogestrel or ethinyl estradiol in the Assay preparation based on the label claim; and rU and rS are the peak responses for desogestrel or ethinyl estradiol obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Domenick Vicchio, Ph.D.
Senior Scientific Liaison 1-301-998-6828 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 2830
Pharmacopeial Forum: Volume No. 30(5) Page 1604