Letrozole

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₇H₁₁N₅ 285.30

Benzonitrile, 4,4′-(1H-1,2,4-triazol-1-ylmethylene)bis-;

4,4′-(1H-1,2,4-Triazol-1-ylmethylene)dibenzonitrile CAS RN®: 112809-51-5; UNII: 7LKK855W8I.

1 DEFINITION

Letrozole contains NLT 98.0% and NMT 102.0% of C₁₇H₁₁N₅, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See the gradient table below.

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

(See Chromatography 〈621〉, System Suitability.)

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 = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Letrozole RS in the Standard solution (mg/mL)

C_U = nominal concentration of letrozole in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

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 = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of letrozole from the Standard solution

C_S = concentration of USP Letrozole RS in the Standard solution (mg/mL)

C_U = concentration of Letrozole in the Sample solution (mg/mL)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total unspecified impurities: NMT 0.3%

Impurity Table 1

^a 4,4′-(1H-1,3,4-triazol-1-ylmethylene)dibenzonitrile.

[Note—Disregard any impurity peaks less than 0.05%.]

5 SPECIFIC TESTS

Water Determination, Method I〈921〉: NMT 0.3%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers at controlled room temperature.

USP Reference Standards 〈11〉

USP Letrozole RS

USP Letrozole Related Compound A RS

4,4′-(1H-1,3,4-Triazol-1-ylmethylene)dibenzonitrile.

C₁₇H₁₁N₅ 285.31