Levonorgestrel and Ethinylestradiol Tablets

Edition: BP 2025 (Ph. Eur. 11.6 update)

Action and use

Progestogen.

DEFINITION

Levonorgestrel and Ethinylestradiol Tablets contain Levonorgestrel and Ethinylestradiol.

The tablets comply with the requirements stated under Tablets and with the following requirements. For Levonorgestrel and Ethinylestradiol Tablets presented in 21-day or 28-day calendar packs, apply the requirements separately to tablets of each combination of different proportions, by weight, of the active ingredients. Where applicable, disregard any tablets that contain no active ingredient (placebo tablets).

Content of levonorgestrel, C₂₁H₂₈O₂

90.0 to 110.0% of the stated amount.

Content of ethinylestradiol, C₂₀H₂₄O₂

90.0 to 110.0% of the stated amount.

IDENTIFICATION

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Extract 15 powdered tablets with 30 mL of acetone, filter, evaporate to dryness and dissolve the residue in 1 mL of chloroform.

(2) 0.075% w/v of levonorgestrel BPCRS in chloroform.

(3) 0.045% w/v of ethinylestradiol BPCRS in chloroform.

CHROMATOGRAPHIC CONDITIONS

(a) Use as the coating silica gel GF254.

(b) Use the mobile phase as described below.

(c) Apply 20 μL of each solution.

(d) Develop the plate to 15 cm. Develop the chromatograms twice, drying the plates between developments.

(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm).

(f) Spray the plate with a 2% w/v solution of toluene-p-sulfonic acid in water and heat at 105° for 10 minutes and examine under ultraviolet light (365 nm).

MOBILE PHASE

1 volume of methanol and 99 volumes of chloroform.

CONFIRMATION

By the first method of visualisation:

one of the principal spots in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2) and the other principal spot corresponds to that in the chromatogram obtained with solution (3).

By the second method of visualisation:

the spots corresponding to levonorgestrel and ethinylestradiol appear as blue spots.

Uniformity of content

Prepare the following stock solutions using a mixture of 40 volumes of water and 60 volumes of acetonitrile.

Solution A 0.0625% w/v of levonorgestrel BPCRS.

Solution B 0.025% of ethinylestradiol BPCRS.

Solution C 0.020% w/v of 2-hydroxybiphenyl (internal standard).

Solution D Dilute 1 mL of solution C to 20 mL with the solvent mixture.

Tablets containing less than 2 mg and/or less than 2% w/w of Levonorgestrel or less than 2 mg and/or less than 2% w/w of Ethinylestradiol 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.

(1) Add 4 mL of solution D to one tablet, heat at 60° in an ultrasonic bath for 25 minutes, shake and repeat the ultrasound treatment. Cool, centrifuge and use the clear supernatant liquid.

(2) Mix the volumes of solutions A and B specified in the table with 5 mL of solution C and dilute to 100 mL with a mixture of 40 volumes of water and 60 volumes of acetonitrile.

CHROMATOGRAPHIC CONDITIONS

(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Hypersil ODS is suitable).

(b) Use isocratic elution and the mobile phase described below.

(c) Use a flow rate of 1.5 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 215 nm.

(f) Inject 20 μL of each solution.

MOBILE PHASE

49 volumes of acetonitrile and 51 volumes of water.

DETERMINATION OF CONTENT

Calculate the content of C₂₁H₂₈O₂ and of C₂₀H₂₄O₂ in each tablet using the declared content of C₂₁H₂₈O₂ in levonorgestrel BPCRS and the declared content of C₂₀H₂₄O₂ in ethinylestradiol BPCRS.

ASSAY

For both levonorgestrel and ethinylestradiol use the average of the individual results determined in the test for Uniformity of content.