Letrozole Tablets

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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1 DEFINITION

Letrozole Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of letrozole (C₁₇H₁₁N₅ ).

2 IDENTIFICATION

A. Thin-Layer Chromatographic Identification Test 〈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)

Acceptance criteria: Meet the requirements

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

Mobile phase: Acetonitrile and water (48:52)

Diluent: Acetonitrile and water (30:70)

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 the 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 the Sample stock solution

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 volume: 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 the labeled amount of letrozole (C₁₇H₁₁N₅ ) in the portion of Tablets taken:

Result = (r_U/r_S) × (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 (μg/mL)

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

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 100 rpm

Time: 30 min

Standard solution: Transfer USP Letrozole RS to a suitable volumetric flask, dissolve in acetonitrile equivalent to 10% of the final volume, and dilute with Medium to volume to obtain a solution of 0.05 mg/mL of letrozole. Dilute this solution with Medium to obtain a solution of 0.005 mg/mL of letrozole.

Sample solution: Centrifuge a portion of the solution under test at 4000 rpm for 5 min.

Mobile phase and Chromatographic system: Proceed as directed in the Assay, except use an injection volume of 200 μL.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of letrozole (C₁₇H₁₁N₅ ) dissolved:

Result = (r_U/r_S)x(C_S /L) × V × 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)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of letrozole (C₁₇H₁₁N₅ ) is dissolved.

Test 2

Medium: 0.1 N hydrochloric acid solution adjusted with 50% sodium hydroxide (NaOH) to a pH of 1.2; 900 mL, deaerated

Apparatus 2: 75 rpm

Time: 30 min

Mobile phase: Acetonitrile and water (45:55)

Standard stock solution: 0.3 mg/mL of USP Letrozole RS in Mobile phase

Standard solution: 3.0 μg/mL of USP Letrozole RS in Medium from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 35-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 100 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of letrozole (C₁₇H₁₁N₅ ) dissolved:

Result = (r_U/r_S)x(C_S /L) × V × 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)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of letrozole (C₁₇H₁₁N₅ ) is dissolved.

Test 3

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 75 rpm

Time: 30 min

Mobile phase: Acetonitrile and water (48:52)

Standard stock solution: 0.25 mg/mL of USP Letrozole RS in Mobile phase

Standard solution: 0.005 mg/mL of USP Letrozole RS in Medium from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size and discard the first few mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 50 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 the labeled amount of letrozole (C₁₇H₁₁N₅ ) dissolved:

Result = (r_U/r_S)x(C_S/L) × V × 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)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of letrozole (C₁₇H₁₁N₅ ) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Prepare as directed in the Assay.

System suitability solution: 10 μg/mL of USP Letrozole RS and 2 μg/mL of USP Letrozole Related Compound A 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: Nominally 0.1 mg/mL of letrozole in Diluent. Shake the whole Tablets (NLT 10) for about 15 min in a portion of Diluent to aid in dissolution. Centrifuge, and use the supernatant.

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 volume: 50 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between letrozole and letrozole related compound A, 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 = (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 = nominal concentration of letrozole in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any impurity peaks less than 0.05%.

Table 2

^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 controlled in the drug substance

monograph.]

6 ADDITIONAL REQUIREMENTS

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

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

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