Estradiol Transdermal System
DEFINITION
Change to read:
Estradiol Transdermal System contains 
NLT 85.0% and NMT 120.0%(RB 1-May-2011) of the labeled amount of estradiol (C18H24O2).
NLT 85.0% and NMT 120.0%(RB 1-May-2011) of the labeled amount of estradiol (C18H24O2).IDENTIFICATION
• A.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
Change to read:
• Procedure
Diluent:
Acetonitrile and water (1:1)
Mobile phase:
Acetonitrile and water (55:45)
Standard solution:
0.1 mg/mL of USP Estradiol RS in Diluent
Sample solutions:
Equivalent to 0.1 mg/mL of estradiol in Diluent, prepared as follows. Cut 10 Transdermal Systems into pieces, and keep the pieces from each system separate. Remove and discard the protective liners, if present, from the strips. Transfer the pieces of each system into separate stoppered flasks of suitable size, and add a measured volume of Diluent to each flask to provide the target estradiol concentration. Shake by mechanical means for about 3 h, and sonicate for 15 min.
Chromatographic system
Mode:
LC
Detector:
UV 280 nm
Column:
4.6-mm × 15-cm; packing L1
Column temperature:
35
Flow rate:
1 mL/min
Injection size:
25 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
0.9–1.6
Relative standard deviation:
NMT 2.5%
Analysis
Samples:
Standard solution and Sample solutions
Calculate the percentage of estradiol (C18H24O2) in each Transdermal System 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 Estradiol RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of estradiol in the Sample solution (mg/mL) |
Use the individual assays to determine Uniformity of Dosage Units.
Acceptance criteria:
85.0%–120.0%(RB 1-May-2011)
85.0%–120.0%(RB 1-May-2011)
OTHER COMPONENTS
• Alcohol Content (if present)
Diluent:
Acetonitrile and water (1:1)
Internal standard solution:
Prepare by diluting 4.0 mL of dehydrated methanol with water to 100 mL.
Standard stock solution:
5.0 mg/mL of ethanol in Diluent. Prepare by weighing by difference 1.6 mL of dehydrated alcohol into a tared 50-mL volumetric flask containing 15 mL of water, and dilute with Diluent to volume. Pipet 10.0 mL of this solution into a 50-mL volumetric flask, and dilute with Diluent to volume.
Standard solution:
2.5 mg/mL of ethanol. Prepare by pipeting 25.0 mL of the Standard stock solution into a 50-mL volumetric flask. Add 5.0 mL of the Internal standard solution, and dilute with water to volume.
Sample solutions:
Prepare as directed for the Sample solutions in the Assay, with the following changes. Pipet 25.0 mL of each solution into individual 50-mL volumetric flasks. Add 5.0 mL of the Internal standard solution, and dilute with water to volume.
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
2-mm × 2-m glass; support S2
Temperature
Column:
100
Injection port:
200
Detector:
200
Carrier gas:
Helium
Flow rate:
30 mL/min
Injection size:
2 µL
System suitability
Sample:
Standard solution
[Note—The relative retention times for the methanol and alcohol peaks are 0.4 and 1.0, respectively. ]
Suitability requirements
Relative standard deviation:
NMT 1.5% from the peak response ratio of alcohol to methanol
Analysis
Samples:
Standard solution and Sample solutions
Calculate the percentage of alcohol (C2H5OH) in each Transdermal System taken:
Result = (RU/RS) × (CS/CU) × 100
| RU | = | = peak response ratio of alcohol to methanol from the Sample solution |
| RS | = | = peak response ratio of alcohol to methanol from the Standard solution |
| CS | = | = concentration of dehydrated alcohol in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of alcohol in the Sample solution (mg/mL) |
Average the percentage of alcohol found in the Transdermal Systems analyzed.
Acceptance criteria:
80%–120% of the labeled amount of C2H5OH
PERFORMANCE TESTS
• Uniformity of Dosage Units 
905
:
The results from the Transdermal Systems used in the Assay meet the requirements.
905:
The results from the Transdermal Systems used in the Assay meet the requirements.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in hermetic, light-resistant, unit-dose pouches.
• Labeling:
The label states the total amount of estradiol in the Transdermal System and the release rate, in mg/day, for the duration of application of one system.
• USP Reference Standards 11
11
USP Estradiol RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Domenick Vicchio, Ph.D.
Senior Scientific Liaison 1-301-998-6828 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3105
Pharmacopeial Forum: Volume No. 35(5) Page 1136