Action and use
Progestogen.
Definition
Megestrol Tablets contain Megestrol Acetate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of megestrol acetate, C24H32O4
92.5 to 107.5% of the stated amount.
Identification
Shake a quantity of the powdered tablets containing 40 mg of Megestrol Acetate with 250 mL of chloroform for 30 minutes, filter into a separating funnel, wash the filtrate with 20 mL of water and evaporate the chloroform. The residue, after drying at 60° at a pressure not exceeding 0.7 kPa for 2 hours, complies with the following tests.
Tests
Disintegration
Maximum time, 30 minutes, Appendix XII A1.
Related foreign steroids
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 100 mg of Megestrol Acetate with 10 mL of a mixture of 1 volume of
methanol and 9 volumes of
chloroform for 10 minutes, centrifuge and use the clear supernatant liquid.
(2) 0.005% w/v of
megestrol BPCRS in a mixture of 1 volume of
methanol and 9 volumes of
chloroform.
chromatographic conditions
(a) Use a silica gel precoated plate (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 15 cm.
mobile phase
0.5 volume of water, 8 volumes of methanol and 92 volumes of 1,2-dichloroethane.
limits
Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%).
Assay
Prepare a 0.016% w/v solution of propyl 4-hydroxybenzoate (internal standard) in acetonitrile (solution A).
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 80 mg of Megestrol Acetate with 10 mL of
water for 10 minutes, add 75 mL of
acetonitrile, shake for 30 minutes, dilute to 100 mL with
acetonitrile, centrifuge and dilute 10 mL of the clear supernatant liquid to 50 mL with a 40% v/v solution of
acetonitrile; to 5 mL of this solution add 10 mL of
acetonitrile and dilute to 50 mL with a 40% v/v solution of
acetonitrile.
(2) Mix 4 mL of a 0.02% w/v solution of
megestrol acetate BPCRS in
acetonitrile with 10 mL of solution A and dilute to 50 mL with a 40% v/v solution of
acetonitrile.
(3) Prepare solution (3) in the same manner as solution (1) but adding 10 mL of solution A in place of the 10 mL of
acetonitrile.
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 280 nm.
(f) Inject 20 µL of each solution.
mobile phase
32 volumes of water and 68 volumes of acetonitrile.
system suitability
The test is not valid unless, in the chromatogram obtained with solution (2), the resolution factor between the peaks due to propyl 4-hydroxybenzoate and megestrol acetate is at least 8.0.
determination of content
Calculate the content of C24H32O4 in the tablets using the declared content of C24H32O4 in megestrol acetate BPCRS.