Anastrozole

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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C₁₇H₁₉N₅          293.37

1,3-Benzenediacetonitrile, a,a,a', a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-;a,a,a',a'-Tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile CAS RN: 120511-73-1; UNII: 2Z07MYW1AZ.

1 DEFINITION

Anastrozole contains NLT 98.0% and NMT 102.0% of anastrozole (CHN), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN1-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: Acetonitrile, methanol, trifluoroacetic acid, and water (100:300:0.5:600)

Solution B: Acetonitrile, methanol, trifluoroacetic acid, and water (150:450:0.5:400)

Mobile phase: See Table 1.

Table 1

[NOTE-These gradient elution times are established on an HPLC system with a dwell time of approximately 0 min. The gradient elution times in the table can be adjusted by subtracting the dwell time to achieve the separation described.]

Standard solution: 0.5 mg/mL of USP Anastrozole RS prepared as follows. Transfer USP Anastrozole RS into a suitable volumetric flask.

Dissolve in acetonitrile, using 40% of the final volume, and then dilute with Solution A to volume.

Sample solution: 0.5 mg/mL of Anastrozole prepared as follows. Transfer 25 mg of Anastrozole to a 50-mL volumetric flask, add 20 mL of acetonitrile to dissolve. Dilute with Solution A to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 3.2-mm x 10-cm; 5-µm packing L42

Flow rate: 0.75 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: Between 0.9 and 1.4

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of anastrozole (C₁₇H₁₉N₅) in the portion of Anastrozole taken:

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

r_u = peak area of anastrozole from the Sample solution

r_s = peak area of anastrozole from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

Solution A, Solution B, and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution: 0.2 mg/mL of USP Anastrozole RS prepared as follows. Dissolve in acetonitrile, using 40% of the final volume, and then dilute with Solution A to volume.

Standard solution: 0.02 mg/mL of USP Anastrozole RS in Solution A from the Standard stock solution

Sample solution: 2 mg/mL of Anastrozole prepared as follows. Transfer 50 mg of Anastrozole to a 25-mL volumetric flask. Add 10 mL of acetonitrile. Dissolve in and dilute with Solution A to volume.

Blank solution: Transfer 10 mL of acetonitrile into a 25-mL volumetric flask, and dilute with Solution A to volume.

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: Between 0.9 and 1.4

Relative standard deviation: NMT 5%

Analysis

Samples: Standard solution, Sample solution, and Blank solution. [NOTE-Adjust the peak areas for any interference from the Blank solution.]

Calculate the percentage of each individual impurity in the portion of Anastrozole taken:

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

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

r_s = peak area of anastrozole from the Standard solution S

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

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

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

Table 2

^a 2-(3-(1-Cyanoethyl)-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl)-2-methylpropionitrile.

^b 2,3-Bis(3-(1-cyano-1-methylethyl)-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl)-2-methylpropionitrile.

^c 2,2′-(5-(Bromomethyl)-1,3-phenylene)bis(2-methylpropionitrile).

^d 2,2′-(5-(Dibromomethyl)-1,3-phenylene)bis(2-methylpropionitrile).

5 SPECIFIC TESTS

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Anastrozole RS