Megestrol Acetate Oral Suspension
DEFINITION
Megestrol Acetate Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of megestrol acetate (C24H32O4).
IDENTIFICATION
• Thin-Layer Chromatographic Identification Test 
201
201
Standard solution:
4.0 mg/mL of USP Megestrol Acetate RS in chloroform
Sample solution:
Transfer Oral Suspension, equivalent to 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.
Developing solvent system:
Chloroform and ethyl acetate (4:1)
ASSAY
• Procedure
Mobile phase:
Acetonitrile and water (11:9)
Standard solution:
80 µg/mL of USP Megestrol Acetate RS in Mobile phase
Sample solution:
A volume of Oral Suspension diluted with Mobile phase to obtain nominally 80 µg/mL of megestrol acetate
Chromatographic system
Mode:
LC
Detector:
UV 280 nm
Column:
3.9-mm × 30-cm; packing L1
Flow rate:
1.5 mL/min
Injection size:
25 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 2500 theoretical plates
Tailing factor:
NMT 1.4
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C24H32O4 in the portion of Oral Suspension taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Megestrol Acetate RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of the Sample solution (µg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Test 1
Medium:
0.5% sodium lauryl sulfate in water; 900 mL
Apparatus 2:
25 rpm
Time:
30 min
Detector:
UV 292 nm
Standard solution:
45 mg of USP Megestrol Acetate RS in a 250-mL volumetric flask. Add 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 180 µg/mL of megestrol acetate. Dilute with Medium, if necessary.
Sample solution:
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 160 mg of megestrol acetate. At the sampling time, withdraw a volume of the solution under test and pass through a suitable filter with 0.45-µm pore size. Dilute with Medium, if necessary.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C24H32O4 released:
Result = (AU/AS) × (CS/V) × VD × (100/L)
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = volume of Oral Suspension taken |
| VD | = | = volume of Medium, 900 mL |
| L | = | = label claim (mg/mL) |
Tolerances:
NLT 80% (Q) of the labeled amount of C24H32O4 is dissolved.
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 min
Detector:
UV 292 nm, using 0.5-cm pathlength cuvettes
Standard solution:
45 mg of USP Megestrol Acetate RS in a 250-mL volumetric flask. Add 5 mL of methanol. 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 18 µg/mL.
Sample 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 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. Weigh each syringe after dispensing the sample (tare weight). Record sample weights. After completion of the dissolution, pass an aliquot through a suitable nylon filter with 0.45 µm pore size, 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/mL.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C24H32O4 released:
Result = (AU/AS) × (CS/W) × VD × d × (100/L)
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| W | = | = weight of the Oral Suspension taken (mg) |
| VD | = | = volume of the Medium in the dissolution vessel, 900 mL |
| d | = | = density of the Oral Suspension (mg/mL), obtained by dividing the weight of Oral Suspension taken by 10 mL |
| L | = | = label claim (mg/mL) |
Tolerances:
NLT 80% (Q) of the labeled amount of C24H32O4 is dissolved.
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. [Note—Use ultrapure sodium lauryl sulfate with an Assay content of NLT 99.0%. ]
Apparatus 2:
50 rpm
Time:
30 min
Determine the amount of C24H32O4 dissolved by using the following method.
Mobile phase:
Proceed as directed in the Assay.
Standard solution:
0.46 mg/mL of USP Megestrol Acetate RS in Mobile phase
Sample solution:
Proceed as directed for Test 2, introducing the sample into the vessel over a 10- to 15-s period (about 1 mL/s).
Chromatographic system:
Proceed as directed in the Assay.
Injection size:
10 µL
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C24H32O4 released:
Result = (rU/rS) × (CS/W) × VD × d × (100/L)
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| W | = | = weight of the Oral Suspension taken (mg) |
| VD | = | = volume of the Medium in the dissolution vessel, 900 mL |
| d | = | = density of the Oral Suspension (mg/mL), obtained by dividing the weight of Oral Suspension taken by 10 mL |
| L | = | = label claim (mg/mL) |
Tolerances:
NLT 80% (Q) of the labeled amount of C24H32O4 is dissolved.
• Deliverable Volume 698:
Meets the requirements
698:
Meets the requirements
SPECIFIC TESTS
• pH 791:
3.0–4.7
791:
3.0–4.7
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed, light-resistant containers.
• Labeling:
When more than one test for Dissolution is given, the labeling states the test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Megestrol Acetate RS 
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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 3786
Pharmacopeial Forum: Volume No. 35(1) Page 75