Norethindrone Acetate and Ethinyl Estradiol Tablets
DEFINITION
Norethindrone Acetate and Ethinyl Estradiol Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of norethindrone acetate (C22H28O3), and NLT 88.0% and NMT 112.0% of the labeled amount of ethinyl estradiol (C20H24O2).
IDENTIFICATION
A.
The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Mobile phase:
Acetonitrile, methanol, and water (40:5:55)
Diluent:
Acetonitrile and water (1:1)
Standard solution:
90 µg/mL of USP Norethindrone Acetate RS and 1.76 µg/mL of USP Ethinyl Estradiol RS in Diluent
Sample solution:
Transfer an appropriate number of Tablets, NLT 20, to a volumetric flask, such that the final concentration is 100 µg/mL of norethindrone acetate based on the label claim. Fill the flask with Diluent to about 75% of volume, and disintegrate the Tablets by mechanical shaking and sonication. Allow the solution to equilibrate to room temperature, and dilute with Diluent to volume. Centrifuge a portion of the solution using glass centrifuge tubes, and use the clear supernatant.
Chromatographic system
Mode:
LC
Detector:
UV 200 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.5 mL/min
Injection size:
100 µL
System suitability
Sample:
Standard solution
[Note—The relative retention times for ethinyl estradiol and norethindrone acetate are about 0.28 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 10.0 between ethinyl estradiol and norethindrone acetate
Tailing factor:
NMT 2.0 for ethinyl estradiol and norethindrone acetate
Relative standard deviation:
NMT 2.0% for ethinyl estradiol and norethindrone acetate
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of norethindrone acetate (C22H28O3) and ethinyl estradiol (C20H24O2) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of the corresponding analyte from the Sample solution |
| rS | = | = peak response of the corresponding analyte from the Standard solution |
| CS | = | = concentration of the appropriate USP Reference Standard in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of the corresponding analyte in the Sample solution (µg/mL) |
Acceptance criteria:
90.0%–110.0% of the labeled amount of norethindrone acetate (C22H28O3); 88.0%–112.0% of the labeled amount of ethinyl estradiol (C20H24O2)
PERFORMANCE TESTS
• Dissolution 
711
711
0.025 M acetate buffer solution:
Transfer 5.22 g of anhydrous sodium acetate and 2.2 g of glacial acetic acid to a 4-L volumetric flask, add 3.5 mL of water, and adjust with 1 N sodium hydroxide to a pH of 5.0 ± 0.2. Dilute with water to volume.
Medium:
0.025 M acetate buffer solution with 0.15% sodium lauryl sulfate, prepared by weighing 6 g of sodium lauryl sulfate into a 4-L volumetric flask, adding 1.5 L of 0.025 M acetate buffer solution, mixing, and diluting with 0.025 M acetate buffer solution to volume; 600 mL
Apparatus 2:
75 rpm
Time:
60 min
Mobile phase:
0.2% phosphoric acid, acetonitrile, and tetrahydrofuran (540:380:80)
Standard solution:
USP Norethindrone Acetate RS and USP Ethinyl Estradiol RS dissolved in a minimum amount of acetonitrile, and diluted with Medium to obtain a solution having known concentrations equivalent to the expected concentrations of the solution under test
Sample solution:
Withdraw a 2-mL aliquot, using a glass pipet or syringe, and centrifuge at about 2000 rpm for about 5 min. Use the supernatant as the Sample solution.
Chromatographic system
Mode:
LC
Detector:
UV 242 nm detector and a fluorescence detector with an excitation wavelength set at 210 nm and an emission wavelength set at 310 nm
Column:
6-mm × 40-mm; 3-µm packing L1
Guard column:
4-mm × 12.5-mm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
200 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 500 theoretical plates for ethinyl estradiol and NLT 1400 theoretical plates for norethindrone acetate
Tailing factor:
NMT 2.0 for norethindrone acetate and ethinyl estradiol
Relative standard deviation:
NMT 2.5% for norethindrone acetate and ethinyl estradiol
Analysis
Samples:
Standard solution and Sample solution
Tolerances:
NLT 80% (Q) of the labeled amounts of norethindrone acetate (C22H28O3) and ethinyl estradiol (C20H24O2) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
') + '&img=../../images/v35300/cas-57-63-6.gif',600,500);)
') + '&img=../../images/v35300/cas-51-98-9.gif',600,500);)
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Mary S. Waddell
Scientific Liaison 1-301-816-8124 |
(SM42010) Monographs - Small Molecules 4 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4080
Pharmacopeial Forum: Volume No. 36(5) Page 1195