Letrozole
C17H11N5 285.31
Benzonitrile, 4,4¢-(1H-1,2,4-triazol-1-ylmethylene)bis-;
4,4¢-(1H-1,2,4-Triazol-1-ylmethylene)dibenzonitrile
[112809-51-5].
(let' roe zole).
+'&img=../../images/v35300/g-1606.gif&casNumber=112809-51-5&usp=35&nf=30&chemicalStructureImage=true&ID='+parent.myID,600,500);)
C17H11N5 285.31
Benzonitrile, 4,4¢-(1H-1,2,4-triazol-1-ylmethylene)bis-;
4,4¢-(1H-1,2,4-Triazol-1-ylmethylene)dibenzonitrile
[112809-51-5].DEFINITION
Letrozole contains NLT 98.0% and NMT 102.0% of C17H11N5, calculated on the anhydrous basis.
IDENTIFICATION
• 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
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:
Acetonitrile and water (3:7)
Standard solution:
10 µg/mL of USP Letrozole RS in Diluent. [Note—Dissolve USP Letrozole RS in acetonitrile, then dilute with water. ]
Sample solution:
10 µg/mL of Letrozole in Diluent. [Note—Dissolve Letrozole in acetonitrile, then dilute with water. ]
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 Letrozole 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 (mg/mL) |
| CU | = | = nominal concentration of letrozole in the Sample solution (mg/mL) |
Acceptance criteria:
98.0%–102.0% on the anhydrous basis
IMPURITIES
Organic Impurities
• Procedure
Solution A, Solution B, Mobile phase, Chromatographic system, and Diluent:
Proceed as directed in the Assay.
System suitability solution:
2 µg/mL of USP Letrozole Related Compound A RS and 10 µg/mL of USP Letrozole RS in Diluent. [Note—Dissolve Letrozole and USP Letrozole Related Compound A RS in acetonitrile, then dilute with water. ]
Standard solution:
1 µg/mL of USP Letrozole RS in Diluent. [Note—Dissolve USP Letrozole RS in acetonitrile, then dilute with water. ]
Sample solution:
Transfer 25 mg of Letrozole to a 250-mL volumetric flask. Dissolve in 75 mL of acetonitrile, and dilute with water to volume.
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%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Letrozole 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 | = | = concentration of Letrozole in the Sample solution (mg/mL) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total unspecified impurities:
NMT 0.3%
[Note—Disregard any impurity peaks less than 0.05%. ]
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Letrozole related compound Aa | 0.67 | 0.3 |
| Letrozole | 1.0 | — |
| 4,4',4''-Methanetriyltribenzonitrile | 2.4 | 0.2 |
| Any unspecified impurity | — | 0.1 |
|
a
4,4¢-(1H-1,3,4-triazol-1-ylmethylene)dibenzonitrile.
|
||
SPECIFIC TESTS
• Water Determination, Method I 
921
:
NMT 0.3%
921:
NMT 0.3%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers at controlled room temperature.
• USP Reference Standards 11
11
USP Letrozole RS 
') + '&img=../../images/v35300/cas-112809-51-5.gif',600,500);)
USP Letrozole Related Compound A RS
4,4¢-(1H-1,3,4-Triazol-1-ylmethylene)dibenzonitrile.
C17H11N5 285.31
') + '&img=../../images/v35300/c11rs1519.gif',600,500);)
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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3647
Pharmacopeial Forum: Volume No. 36(1) Page 111