Letrozole Tablets
DEFINITION
Letrozole Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of letrozole (C17H11N5).
IDENTIFICATION
• A. Thin-Layer Chromatographic Identification Test 
201
201
Sample solution:
Equivalent to 2 mg/mL of letrozole from powdered Tablets in methanol. [Note—Shake thoroughly, sonicate for 10 min, and centrifuge. ]
Application volume:
5 µL
Developing solvent system:
Ethyl acetate and methanol (9:1)
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Mobile phase:
Acetonitrile and water (12:13)
Diluent:
Acetonitrile and water (3:7)
Standard stock solution:
0.2 mg/mL of USP Letrozole RS in Diluent. [Note—Dissolve letrozole in acetonitrile and then dilute with water. ]
Standard solution:
10 µg/mL of USP Letrozole RS in Mobile phase, from Standard stock solution
Sample stock solution:
Equivalent to 50 mg of letrozole from Tablets, in a 250-mL volumetric flask. Add 20 mL of water, and shake for 5 min to dissolve the Tablets. Add 75 mL of acetonitrile, shake for 30 min, and dilute with water to volume. Centrifuge a portion of the solution.
Sample solution:
10 µg/mL of letrozole in Mobile phase, from Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 12.5-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
0.8–1.5
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C17H11N5 in the portion of Tablets 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 Letrozole RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of letrozole in the Sample solution (µg/mL) |
Acceptance criteria:
95.0%–105.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
0.1 N hydrochloric acid; 500 mL
Apparatus 2:
100 rpm
Time:
30 min
Standard solution:
Transfer 50 mg of USP Letrozole RS to a 1-L volumetric flask, dissolve in 100 mL of acetonitrile, and dilute with Medium to volume. Dilute this solution with Medium to obtain a final concentration of 0.005 mg/mL.
Sample solution:
Centrifuge a portion of the solution under test at 4000 rpm for 5 min.
Mobile phase and Chromatographic system:
Prepare as directed in the Assay, except to use an injection volume of 200 µL.
Analysis:
Inject a filtered portion of the solution under test into the chromatograph, record the chromatogram, and measure the responses for the major peaks.
Calculate the percentage of letrozole dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| V | = | = volume of Medium, 500 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of C17H11N5 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Solution A:
Water
Solution B:
Acetonitrile
Mobile phase:
See the gradient table below.
| Time
(min) |
Solution A
(%) |
Solution B
(%) |
| 0 | 70 | 30 |
| 25 | 30 | 70 |
Diluent:
Proceed as directed in the Assay.
System suitability solution:
2 µg/mL of USP Letrozole Related Compound A RS, 10 µg/mL of USP Letrozole RS in Diluent. [Note—Dissolve letrozole and letrozole related compound A in acetonitrile, then dilute with water. ]
Standard solution:
1 µg/mL of USP Letrozole RS in Diluent. [Note—Dissolve letrozole in acetonitrile, then dilute with water. ]
Sample solution:
Equivalent to 0.1 mg/mL of letrozole, from dissolved whole tablets in Diluent. [Note—Shake Tablets for about 15 min in a portion of Diluent to aid in dissolution; centrifuge and use the supernatant. ]
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 12.5-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between letrozole related compound A and letrozole, System suitability solution
Relative standard deviation:
NMT 10.0% for letrozole, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of letrozole from the Standard solution |
| CS | = | = concentration of USP Letrozole RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of Letrozole in the Sample solution (mg/mL) |
Acceptance criteria
[Note—Disregard any values obtained that are less than 0.05%. ]
Individual impurities:
See Impurity Table 1.
Total unspecified impurities:
NMT 0.3%
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Letrozole related compound Aa | 0.67 | — |
| Letrozole | 1.0 | — |
| 4,4¢,4¢¢-Methanetriyltribenzonitrile | 2.4 | — |
| Any unspecified impurity | — | 0.1 |
|
a
4,4¢-(1H-1,3,4-Triazol-1-ylmethylene)dibenzonitrile.
[Note—Letrozole related compound A and 4,4',4''-methanetriyltribenzonitrile are process impurities, and are monitored in the drug substance monograph. ]
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers at controlled room temperature.
• USP Reference Standards 11
11
USP Letrozole RS 
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USP Letrozole Related Compound A RS
4,4¢-(1H-1,3,4-Triazol-1-ylmethylene)dibenzonitrile.
C17H11N5 285.31
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4,4¢-(1H-1,3,4-Triazol-1-ylmethylene)dibenzonitrile.
C17H11N5 285.31
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Feiwen Mao, M.S.
Senior Scientific Liaison 1-301-816-8320 |
(SM32010) Monographs - Small Molecules 3 |
| 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 3648
Pharmacopeial Forum: Volume No. 36(1) Page 113