Exemestane

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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C₂₀H₂₄O₂ 296.40

Androsta-1,4-diene-3,17-dione, 6-methylene-;

6-Methyleneandrosta-1,4-diene-3,17-dione CAS RN®: 107868-30-4; UNII: NY22HMQ4BX.

1 DEFINITION

Exemestane contains NLT 97.0% and NMT 102.0% of exemestane (C₂₀H₂₄O₂), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (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

3.1 Procedure

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (1:1)

Standard solution: 0.1 mg/mL of USP Exemestane RS in Diluent

Sample solution: 0.1 mg/mL of Exemestane in Diluent

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 247 nm

Column: 4.6-mm × 15-cm; 3-μm packing L1

Column temperature: 45°

Flow rate: 1.0 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Relative standard deviation: NMT 0.73%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of exemestane (C₂₀H₂₄O₂) in the portion of Exemestane taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of exemestane from the Sample solution

r_S = peak response of exemestane from the Standard solution

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

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

Acceptance criteria: 97.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

4.1 Organic Impurities

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 2. Return to original conditions and re-equilibrate the system.

Table 2

Diluent: Acetonitrile and water (3:1)

System suitability solution: 1 mg/mL of USP Exemestane RS, 0.01 mg/mL of USP Exemestane Related Compound B RS, and 0.01 mg/mL of USP Exemestane Related Compound C RS in Diluent

Sensitivity solution: 0.5 μg/mL each of USP Exemestane RS, USP Exemestane Related Compound B RS, and USP Exemestane Related Compound C RS in Diluent

Standard solution: 5 μg/mL of USP Exemestane RS in Diluent

Sample solution: 1 mg/mL of Exemestane in Diluent. The concentration is calculated on the anhydrous and solvent-free basis.

4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 247 nm

Column: 4.6-mm × 25-cm; 3.5-μm packing L1

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection volume: 10 μL

4.3 System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

4.4 Suitability requirements

Resolution: NLT 2.0 between exemestane related compound B and exemestane related compound C; NLT 2.0 between exemestane related compound C and exemestane, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Signal-to-noise ratio: NLT 10 for the exemestane, exemestane related compound B, and exemestane related compound C peaks, Sensitivity solution

4.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Exemestane taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of exemestane from the Standard solution

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

C_U = concentration of Exemestane in the Sample solution (mg/mL) (the concentration is calculated on the anhydrous and solvent-free basis)

F = relative response factor for each individual impurity (see Table 3)

Acceptance criteria: See Table 3. Disregard any impurity peaks less than 0.05%.

Table 3

Limit of Exemestane Related Compound D

Mobile phase: Hexane, isopropyl alcohol, and diethylamine (90:10:0.1)

System suitability solution: 8 mg/mL of USP Exemestane System Suitability Mixture RS in anhydrous alcohol

Standard solution: 0.04 mg/mL of USP Exemestane RS in anhydrous alcohol

Sensitivity solution: 4 μg/mL of USP Exemestane RS in anhydrous alcohol, from the Standard solution

Sample solution: 8 mg/mL of Exemestane in anhydrous alcohol. The concentration is calculated on the anhydrous and solvent-free basis.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 247 nm

Column: 4.6-mm × 25-cm; 10-μm packing L80

Column temperature: 30°

Flow rate: 1.2 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT than 2.0 between exemestane and exemestane related compound D, System suitability solution

Relative standard deviation: NMT 5%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of exemestane related compound D in the portion of Exemestane taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × 100

r_U = peak response of exemestane related compound D from the Sample solution

r_S = peak response of exemestane from the Standard solution

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

C_U = concentration of Exemestane in the Sample solution (mg/mL) (the concentration is calculated on the anhydrous and solvent-free basis)

F = relative response factor for exemestane related compound D (see Table 4)

Acceptance criteria: See Table 4.

Table 4

Total impurities: NMT 2.5%. Total impurities include the impurities in Table 3 and Table 4.

5 SPECIFIC TESTS

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

Optical Rotation 〈781S〉, Specific Rotation

Sample solution: 10 mg/mL in methanol

Acceptance criteria: +290° to +300° on the anhydrous basis

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Exemestane RS

USP Exemestane Related Compound B RS

6-Hydroxymethylandrosta-1,4-diene-3,17-dione.

C₂₀H₂₆O₃ 314.42

USP Exemestane Related Compound C RS

Androsta-1,4-diene-3,17-dione.

C₁₉H₂₄O₂284.39

USP Exemestane System Suitability Mixture RS

Exemestane containing a small amount of exemestane related compound D (16-Methyleneandrosta-1,4-diene-3,17-dione).

C₂₀H₂₄O₂ 296.40