Test solution— Transfer an accurately measured volume of Oral Suspension, equivalent to about 160 mg of megestrol acetate, to a separatory funnel, add 50 mL of water and 40 mL of chloroform, and shake. Allow the phases to separate, and discard the aqueous layer.

Standard solution— Prepare a solution containing about 4.0 mg of USP Megestrol Acetate RS per mL of chloroform.

Developing solvent system: a mixture of chloroform and ethyl acetate (4:1).

test 1—

Medium: 0.5% sodium lauryl sulfate in water; 900 mL.

Apparatus 2: 25 rpm.

Time: 30 minutes.

Standard solution— Transfer about 45 mg, accurately weighed, of USP Megestrol Acetate RS to a 250-mL volumetric flask, add about 12 mL of methanol, and place the flask in a warm water bath until the solid is dissolved. Dilute with Medium to volume. The final concentration is about 180 µg of megestrol acetate per mL.

Procedure— Transfer to the surface of the Medium in the dissolution vessel an accurately measured volume of Oral Suspension, freshly mixed and free from air bubbles, equivalent to about 160 mg of megestrol acetate. Determine the amount of C24H32O4 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 292 nm on filtered portions of the solution under test, in comparison with the Standard solution. Calculate the percentage of megestrol acetate (C24H32O4) released by the formula: in which AU and AS are the absorbances obtained from the solution under test and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; V is the sample volume, in mL, of Oral Suspension taken; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the label claim, in mg per mL.

Tolerances— Not less than 80% (Q) of the labeled amount of C24H32O4 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: 0.5% sodium lauryl sulfate in water; 900 mL.

Apparatus 2: 25 rpm.

Time: 30 minutes.

Standard solution— Transfer about 45 mg, accurately weighed, of USP Megestrol Acetate RS to a 250-mL volumetric flask. Add about 5 mL of methanol, and mix. Dilute with Medium to volume. Transfer 10 mL of this solution to a 100-mL volumetric flask, and dilute with Medium to volume. The final concentration is about 18 µg per mL.

Test solution— [note—Use a separate syringe for each vessel.] Withdraw more than 10 mL of the Oral Suspension, using a 10-mL syringe with a long cannula. Remove air bubbles from the syringe. Adjust the volume to the 10-mL mark on the syringe, and remove the needle. Wipe the tip of the syringe, and accurately weigh (gross weight). Operate the apparatus, and rapidly dispense the Oral Suspension to the side of the vessel at about halfway from the bottom. Similarly dispense the Oral Suspension into other vessels. Accurately weigh each syringe after dispensing the sample (tare weight). Record sample weights. After completion of the dissolution, pass an aliquot through a nylon filter having a 0.45-µm porosity, and dilute 2.0 mL of the filtrate with Medium to 50.0 mL to obtain a solution having a theoretical concentration of about 18 µg per mL.

Procedure— Determine the amount of C24H32O4 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 292 nm, using 0.5-cm pathlength cuvettes, on the Test solution in comparison with the Standard solution. Calculate the percentage of megestrol acetate (C24H32O4) released by the formula: in which AU and AS are the absorbances obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; d is the density, in mg per mL, of the Oral Suspension obtained by dividing the weight of Oral Suspension taken by 10 mL; WU is the weight, in mg, of Oral Suspension taken; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the label claim, in mg per mL.

Tolerances— Not less than 80% (Q) of the labeled amount of C24H32O4 is dissolved in 30 minutes.

test 3— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 0.5% sodium lauryl sulfate in degassed water; 900 mL. Use ultrapure sodium lauryl sulfate with an assay content of not less than 99.0%.

Apparatus 2: 50 rpm.

Time: 30 minutes.

Mobile phase— Proceed as directed in the Assay.

Standard solution— Transfer about 11.5 mg, accurately weighed, of USP Megestrol Acetate RS to a 25-mL volumetric flask, and dilute with Mobile phase to volume.

Test solution— Proceed as directed for Test 2, introducing the sample into the vessel over a 10- to 15-second period (about 1 mL per second).

Chromatographic system (see Chromatography 621)— Proceed as directed in the Assay.

Procedure— Separately inject equal volumes (about 10 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 megestrol acetate (C24H32O4) released by the formula: in which rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; d is the density, in mg per mL, of the Oral Suspension obtained by dividing the weight of Oral Suspension taken by 10 mL; WU is the weight, in mg, of Oral Suspension taken; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the label claim, in mg per mL.

Tolerances— Not less than 80% (Q) of the labeled amount of C24H32O4 is dissolved in 30 minutes.

Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and water (11:9). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of Megestrol Acetate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 80 µg per mL.

Assay preparation— Transfer an accurately measured volume of Oral Suspension, equivalent to about 160 mg of megestrol acetate, to a 100-mL volumetric flask, and dissolve in and dilute with Mobile phase to volume. Transfer 5.0 mL of the solution so obtained to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 2500 theoretical plates; the tailing factor is not more than 1.4; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 25 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 quantity, in mg, of megestrol acetate (C24H32O4) in the portion of Oral Suspension taken by the formula: in which C is the concentration, in µg per mL, of USP Megestrol Acetate RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.