Anastrozole 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

Anastrozole Tablets contain NLT 90% and NMT 110% of the labeled amount of anastrozole (C₁₇H₁₉N₅).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN 1-MAY-2020)}

Sample: Transfer the finely ground Tablet powder containing 8 mg of anastrozole into a suitable container. Add 10 mL of diethyl ether and sonicate for 5 min. Aspirate the supernatant and pass through a nylon filter of 0.45-µm pore size into another suitable container containing 400 mg of potassium bromide. Evaporate the mixture to dryness under nitrogen. Further dry it under vacuum at 50° for 1 h. Add an additional 400 mg of potassium bromide for preparation of pellet and analysis.

Acceptance criteria: The spectrum obtained from the Sample shows bands at approximately 2235, 1606, 1500, 1359, 1205, 1137, 1013, and 875 cm, similar to the spectrum from the Reference Standard similarly obtained.

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

Mobile phase: Acetonitrile and water (40:60)

Diluent: Acetonitrile and water (50:50)

Standard solution: 40 µg/mL of USP Anastrozole RS in Diluent. Sonication may be used to aid dissolution.

Sample

solution: Nominally equivalent to 40 µg/mL of anastrozole in Diluent, prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask. Add 40% of the flask volume of water, and shake on a rotary shaker for 10 min to disintegrate the Tablets. Add 40% of the flask volume of acetonitrile, and sonicate for 15 min with intermittent shaking, maintaining the sonicator temperature at 25". Dilute with Diluent to volume. Centrifuge a portion of the solution at 3500 rpm for 10 min, and use the clear solution for analysis.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 15-cm; 5-µm packing 11

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of anastrozole (C₁₇H₁₉N₅) in the portion of Tablets taken:

Result = (r_u /r_s) × (C_s /C_u ) × 100

r_u = peak area from the Sample solution

r_s = peak area from the Standard solution

C_s = concentration of USP Anastrozole RS in the Standard solution (mg/mL)

C_u = nominal concentration of anastrozole in the Sample solution (mg/mL)

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: Water; 900 mL, deaerated

Apparatus 2: 50 rpm

Time: 15 min

Mobile phase: Acetonitrile and water (40:60)

Diluent: Acetonitrile and water (50:50)

Standard stock solution: 0.2 mg/mL of USP Anastrozole RS in Diluent

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of (L/1000) mg/mL, where L is the label claim in mg/Tablet.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-um pore size. Discard the first few ml. of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 mm

Column: 4.6-mm x 15-cm; 5-µm packing 11

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of anastrozole (C₁₇H₁₉N₅) dissolved:

Result = (r_u /r_s ) × (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 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 anastrozole (C₁₇H₁₉N₅) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: Water; 1000 mL, deaerated

Apparatus 2: 50 rpm

Time: 15 min

Mobile phase: Acetonitrile, trifluoroacetic acid, and water (300:1:700)

Standard stock solution: 0.2 mg/mL of USP Anastrozole RS prepared as follows. Transfer USP Anastrozole RS into a suitable volumetric flask and add acetonitrile equivalent to 8% of the final volume. Sonicate to dissolve and dilute with water to volume.

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of (L/1000) mg/mL, where L is the label claim in mg/Tablet.

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

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 215 nm

Column: 3.2-mm x 10-cm; 5-µm packing 142

Flow rate: 0.75 mL/min

Injection volume: 100 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.9–1.4

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of anastrozole (C₁₇H₁₉N₅) dissolved:

Result = (r_u /r_s ) × (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 the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 1000 mL

Tolerances: NLT 80% (Q) of the labeled amount of anastrozole (C₁₇H₁₉N₅) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A: Methanol, acetonitrile, trifluoroacetic acid, and water (200:100:0.7:700)

Solution B: Methanol, acetonitrile, trifluoroacetic acid, and water (500:250:0.7:250)

Mobile phase: See Table 1

Table 1

Diluent: Acetonitrile, trifluoroacetic acid, and water (200:0.8:800)

System suitability stock solution: 0.5 mg/mL of USP Anastrozole RS and 0.3 mg/mL of ethyl 4-hydroxybenzoate in Diluent prepared as follows. Transfer USP Anastrozole RS and ethyl 4-hydroxybenzoate into a suitable volumetric flask and add Diluent equivalent to 50% of the final volume. Sonicate to dissolve and dilute with Diluent to volume.

System suitability solution: 10 µg/mL of USP Anastrozole RS and 6 µg/mL of ethyl 4-hydroxybenzoate in Diluent from the System suitability stock solution

Standard stock solution: 0.5 mg/mL of USP Anastrozole RS in Diluent prepared as follows. Transfer USP Anastrozole RS into a suitable volumetric flask and add Diluent equivalent to 50% of the final volume. Sonicate to dissolve and dilute with Diluent to volume.

Standard solution: 10 µg/mL of USP Anastrozole RS in Diluent from the Standard stock solution

Sample solution: Nominally equivalent to 1.0 mg/mL of anastrozole from NLT 25 finely powdered Tablets, prepared as follows. Transfer a weighed quantity of powdered Tablets, equivalent to 10 mg of anastrozole, to a suitable container and add 10.0 mL of Diluent. Sonicate for 30 min and allow to cool to room temperature. Pass through a suitable filter of 0.45-um pore size, and discard the first few mL of the filtrate. If the filtrate is not clear, pass again through a suitable filter of 0.2-µm pore size, and discard the first few mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm.

Column: 3.2-mm x 10-cm; 5-µm packing 142

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Analysis time: 25 min

System suitability

Sample: System suitability solution.

[NOTE-The relative retention times for ethyl 4-hydroxybenzoate and anastrozole are 0.7 and 1.0, respectively.)

Suitability requirements

Resolution: Greater than 4 between the ethyl 4-hydroxybenzoate and anastrozole peaks

Tailing factor: 0.9-1.3 for the anastrozole peak

Relative standard deviation: NMT 5% for the anastrozole peak

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_u /r_s) × (C_s /C_u ) × 100

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

r_s = peak response of anastrozole from the Standard solution

C_s = concentration of USP Anastrozole RS in the Standard solution (mg/mL)

C_u = nominal concentration of anastrozole in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any impurity peak less than 0.1%.

Table 2

^a 2,2'-(5-[(1H-1,2,4-Triazol-1-yl)methyl]-1,3-phenylene)bis(2-methylpropanamide).

^b 2-(3-[(1H-1,2,4-Triazol-1-yl)methyl]-5-(1-amino-2-methyl-1-oxopropan-2-yl)phenyl)-2-methylpropanoic acid.

^c 2-(3-[(1H-1,2,4-Triazol-1-yl)methyl)-5-(2-cyanopropan-2-yl)phenyl)-2-methylpropanamide.

^d 2-(3-(1-Cyanoethyl)-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl)-2-methylpropanenitrile. This process impurity is controlled in the drug substance monograph. It is included in the table for identification only, and it is not to be reported in the total impurities.

^e 2,2'-(5-((1H-1,2,4-Triazol-1-yl)methyl]-1,3-phenylene)bis(2-methylpropanoic acid).

^f 12-(3-[(1H-1,2,4-Triazol-1-yl)methyl]-5-(2-cyanopropan-2-yl)phenyl)-2-methylpropanoic acid.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at controlled room temperature.

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

USP REFERENCE STANDARDS (11)

USP Anastrozole RS