Desogestrel and Ethinyl Estradiol Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Desogestrel and Ethinyl Estradiol Tablets contain NLT 90.0% and NMT 110.0% of the labeled amounts of desogestrel (C₂₂H₃₀O) and ethinyl estradiol (C₂₀H₂₄O₂).

2 IDENTIFICATION

2.1 A. Thin-Layer Chromatographic Identification Test 〈201〉

Standard solution: 0.15 mg/mL of USP Desogestrel RS and 0.03 mg/mL of USP Ethinyl Estradiol RS in ether

Sample 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.

Chromatographic system

• (See Chromatography 〈621〉, Thin-Layer Chromatography.)
• Mode: TLC
• Application volume: 30 µL
• Developing solvent system: Chloroform and alcohol (96:4)
• Spray reagent: Methanol and sulfuric acid (1:1)

Analysis: Proceed as directed in the chapter, and then air-dry. Spray the plate with the Spray reagent, place in an oven at 105° for about 5 min, and examine the plate.

Acceptance criteria: Meet the requirements

2.2 B. The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer: 20 mM potassium phosphate buffer, pH 6.0

Mobile phase: Acetonitrile and Buffer (1:1)

Diluent: Acetonitrile and water (1:1)

Standard stock solution A: 0.3 mg/mL of USP Desogestrel RS in methanol

Standard stock solution B: 0.3 mg/mL of USP Ethinyl Estradiol RS in methanol

Standard solution: 0.6 µg/mL of USP Desogestrel RS and 0.12 µg/mL of USP Ethinyl Estradiol RS in Diluent, prepared by diluting appropriate aliquots of Standard stock solution A and Standard stock solution B with Diluent

Sample solution: Transfer 20 Tablets into a 200-mL volumetric flask. Add about 120 mL of Diluent, and shake for about 30 min. Dilute with Diluent to volume, and mix. Centrifuge a portion of the sample, and dilute with Diluent to obtain a solution nominally containing 0.6 µg/mL of desogestrel.

Chromatographic system

• (See Chromatography (621), System Suitability.)
• Mode: LC
• Detectors
• Desogestrel analysis: UV 210 nm
• Ethinyl estradiol analysis: Spectrofluorometric detector, excitation at 285 nm and emission at 310 nm
• Columns
• Guard: 4.6 - mm * 12.5 - mm packing L11
• Analytical: 4.6-mm x 15-cm; packing L11
• Flow rate: 2 mL/min
• Injection volume: 200 µL

System suitability

• Sample: Standard solution
• [NOTE-The relative retention times for ethinyl estradiol and desogestrel are about 0.2 and 1.0, respectively.]
• Suitability requirements
• Tailing factor: NMT 2.0 for both ethinyl estradiol and desogestrel
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of desogestrel (C₂₂H₃₀O) and ethinyl estradiol (C₂₀H₂₄O₂) in the portion of Tablets taken:

Result =  (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of the relevant analyte from the Sample solution

r_s = peak response of the relevant analyte from the Standard solution S

C_s = concentration of the appropriate USP Reference Standard in the Standard solution (mg/mL)

C_u = nominal concentration of the relevant analyte in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

4.1.1 Test 1

Medium: 0.05% sodium lauryl sulfate with an assay content of NLT 95%; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 20 mM potassium phosphate buffer, pH 6.0

Mobile phase: Acetonitrile and Buffer (1:1)

Standard stock solution A: 0.005 mg/mL of USP Desogestrel RS in Medium prepared as follows. Dissolve a sufficient quantity of USP Desogestrel RS in methanol to obtain a solution containing 0.25 mg/mL of USP Desogestrel RS. Dilute 1.0 mL of this solution with Medium to 50.0 mL.

Standard stock solution B: 0.005 mg/mL of USP Ethinyl Estradiol RS in Medium prepared as follows. Dissolve a sufficient quantity of USP Ethinyl Estradiol RS in methanol to obtain a solution containing 0.25 mg/mL of USP Ethinyl Estradiol RS. Dilute 1.0 mL of this solution with Medium to 50.0 mL.

Standard solution: 0.3 µg/mL of USP Desogestrel RS and 0.06 µg/mL of USP Ethinyl Estradiol RS in Medium, from Standard stock solution A and Standard stock solution B

Sample solution: Sample per Dissolution (711). Centrifuge a portion of the dissolution sample, and use the clear supernatant.

Chromatographic system

• (See Chromatography (621), System Suitability.)
• Mode: LC
• Detectors
• Desogestrel analysis: UV 210 nm
• Ethinyl estradiol analysis: Spectrofluorometric detector, excitation at 285 nm and emission at 310 nm
• Columns
• Guard: 4.6-mm x 12.5-mm; packing L11
• Analytical: 4.6-mm x 15-cm; packing L11
• Flow rate: 2 mL/min
• Injection volume: 200 µL

System suitability

• Sample: Standard solution
• [NOTE-The relative retention times for ethinyl estradiol and for desogestrel are about 0.2 and 1.0, respectively.]
• Suitability requirements
• Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Determine the amounts of desogestrel (C₂₂H₃₀O) and ethinyl estradiol (C₂₀H₂₄O₂) dissolved:

Result = (r_u/r_s) × (C_s/L) × V × 100

r_u = peak response of the relevant analyte from the Sample solution

r_s = peak response of the relevant analyte from the Standard solution

C_s = concentration of the appropriate USP Reference Standard in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of medium, 500 mL

Tolerances: NLT 80% (Q) of each of the labeled amounts of desogestrel (C₂₂H₃₀O) and ethinyl estradiol (C₂₀H₂₄O₂) is dissolved.

4.1.2 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 min

Analysis: Determine the amounts of desogestrel (C₂H₂O) and ethinyl estradiol (C₂H₂O) dissolved by the chromatographic method used in Test 1.

Tolerances: NLT 80% (Q) of each of the labeled amounts of desogestrel (C₂₂H₃₀O) and ethinyl estradiol (C₂₀H₂₄O₂) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements for Content Uniformity for both desogestrel and ethinyl estradiol

5 ADDITIONAL REQUIREMENTS

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.

USP REFERENCE STANDARDS (11)

USP Desogestrel RS

USP Ethinyl Estradiol RS