Fluconazole

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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C₁₃H₁₂F₂N₆O     306.27

1H-1,2,4-Triazole-1-ethanol, 1-(2,4-diuorophenyl)-1-(1H-1,2,4-triazol-1-ylmethyl)-;

2,4-Diuoro-1′,1′-bis(1H-1,2,4-triazol-1-ylmethyl)benzyl alcohol CAS RN®: 86386-73-4.

1 DEFINITION

Fluconazole contains NLT 98.0% and NMT 102.0% of fluconazole (C₁₃H₁₂F₂N₆O), calculated on the dried basis.

2 IDENTIFICATION

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

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 (20:80)

Standard solution: 0.5 mg/mL of USP Flfluconazole RS in Mobile phase

Sample solution: 0.5 mg/mL of Fluconazole in Mobile phase

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

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

Column temperature: 40°

Flow rate: 0.5 mL/min

Injection volume: 20 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluconazole (C₁₃H₁₂F₂N₆O) in the portion of Fluconazole taken:

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

r_U = peak response of fluconazole from the Sample solution

r_S = peak response of fluconazole from the Standard solution

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

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

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

4 IMPURITIES

Change to read:

Organic Impurities

Mobile phase: Acetonitrile and water (20:80)

Standard solution: 10 µg/mL each of USP Flfluconazole RS, USP Flfluconazole Related Compound A RS, USP Flfluconazole Related Compound B RS, and USP Fluconazole Related Compound C RS, dissolved in acetonitrile, and then diluted in Mobile phase

Sample solution: 3 mg/mL of Fluconazole in Mobile phase

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

Column: 4.6-mm × 15-cm; 3.5-µm packing L1

Column temperature: 40°

Flow rate: 0.5 mL/min

Injection volume: 20 µL

4.2 System suitability

Sample: Standard solution

[Note— See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between fluconazole related compound B and fluconazole related compound C

Relative standard deviation: NMT 5.0% for each peak

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fluconazole related compound A, fluconazole related compound B, and fluconazole related compound C in the portion of Fluconazole taken:

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

r_U = peak response of fluconazole related compound A, fluconazole related compound B, or fluconazole related compound C from the Sample solution

r_S = peak response of fluconazole related compound A, fluconazole related compound B, and fluconazole related compound C from the Standard solution

C_S = concentration of USP Flfluconazole Related Compound A RS, USP Flfluconazole Related Compound B RS, and USP Flfluconazole Related Compound C RS in the Standard solution (mg/mL)

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

Calculate the percentage of any other specified and (ERR 1-Nov-2024) unspecified impurity in the portion of Fluconazole taken:

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

r_U = peak response of anyother specified and unspecified (ERR 1-Nov-2024) impurity from the Sample solution

r_S = peak response of fluconazole from the Standard solution

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

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

Acceptance criteria: See Table 1.

Table 1

Residue on Ignition 〈281〉

Sample: 0.5 g

Acceptance criteria: NMT 0.1%

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store below 30°.

USP Reference Standards 〈11〉

USP Flfluconazole RS

USP Flfluconazole Related Compound A RS

2-[2-Fluoro-4-(1H-1,2,4-triazol-1-yl)phenyl]-1,3-bis(1H-1,2,4-triazol-1-yl)-propan-2-ol.

C₁₅H₁₄FN₉O      355.33

USP Flfluconazole Related Compound B RS

2-(4-Fluorophenyl)-1,3-di(1H-1,2,4-triazol-1-yl)-propan-2-ol.

C₁₃H₁₃FN₆O     288.28

USP Flfluconazole Related Compound C RS

1,1′-(1,3-Phenylene)di(1H-1,2,4-triazole).

C₁₀H₈N₆         212.21