Fluconazole 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

Fluconazole Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV absorption spectrum of the major peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the corresponding peak of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 2.89 g of tetramethyl ammonium bromide and 0.51 g of sodium acetate trihydrate in 750 mL of water. Adjust with glacial acetic acid to a pH of 5.0. Pass through a suitable filter of 0.45-µm pore size.

Mobile phase: Acetonitrile, water, and Buffer (22:15:75)

Diluent: Methanol and water (30:70)

Standard solution: 0.4 mg/mL of USP Fluconazole RS in Diluent. Sonicate if necessary to dissolve.

Sample stock solution: Nominally 2–4 mg/mL of fluconazole prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric ask, add water up to 10% of the ask volume and swirl to disperse the tablets. Add an additional 60% of the ask volume of Diluent and sonicate for 45 min with intermittent shaking. Dilute with Diluent to volume. Centrifuge a suitable portion of this solution for 15 min.

Sample solution: Nominally 0.4 mg/mL of fluconazole in Diluent from Sample stock solution. Pass through a suitable filter of 0.45-µm pore size.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 261 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 40 µL

Run time: NLT 1.5 times the retention time of the fluconazole peak

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 the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O) in the portion of Tablets taken:

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

r_U = peak response of fluconazole from the Sample solution

r_U = peak response of fluconazole from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

4.1 Test 1

Medium: Water; 500 mL (900 mL for Tablets labeled to contain more than 100 mg)

Apparatus 2: 50 rpm

Time: 45 min

Buffer: 0.01 M anhydrous sodium acetate solution. Adjust with glacial acetic acid to a pH of 5.0.

Mobile phase: Methanol, acetonitrile, and Buffer (20:10:70)

Standard solution: 2 mg/mL of USP Fluconazole RS in Medium. Sonicate the solution to facilitate dissolution, if necessary. Quantitatively dilute a portion of this solution with Medium to obtain a nal concentration similar to the one expected in the Sample solution. Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 261 nm

Column: 3.9-mm × 15-cm; 4-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

4.1.2 System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1100 theoretical plates

Tailing factor: NMT 3.0

Relative standard deviation: NMT 2.0%

4.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O) dissolved:

Result = (r_U /r_S) × (C_S /L) × V × 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)

L = label claim (mg/Tablet)

V = volume of Medium, 500 or 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O) is dissolved.

4.2 Test 2

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

Medium: Water; 900 mL (for all Tablet strengths)

Apparatus 2: 50 rpm

Time: 45 min

Mobile phase: Water and acetonitrile (4:1)

Standard stock solution: 1.1 mg/mL of USP Fluconazole RS in methanol

Standard solution: Dilute the Standard stock solution with Medium to obtain a nal concentration of (L/900) 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.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

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

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 50 µL

4.2.2 System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1000 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

4.2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O) dissolved:

Result = (r_U /r_S) × (C_S /L) × V × 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 the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O) is dissolved.

4.3 Test 3

If the product complies with this test, the labeling indicates that it meets Dissolution Test 3.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 3.9 g/L of sodium dihydrogen phosphate in water

Mobile phase: Methanol and Buffer (45:55). Adjust the pH of the solution to 7.0 with 0.1 N sodium hydroxide solution. Standard stock solution: 1.0 mg/mL of USP Fluconazole RS in Mobile phase

Standard solution: (L/900) mg/mL of USP Fluconazole RS in Medium from the Standard stock solution, where L is the Tablet label claim in milligrams

Sample solution: Pass a portion of the solution under test through a suitable filter.

4.3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 50 µL

Run time: At least 2 times the retention time of fluconazole

4.3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluconazole (C₁₃H₁₂F₂N₆O) dissolved:

Result = (r_U /r_S) × (C_S /L) × V × 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)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

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

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A: Acetonitrile and water (15:85)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Peak identification solution: 0.01 mg/mL of USP Fluconazole RS and 6.0 µg/mL each of USP Fluconazole Related Compound A RS, USP Fluconazole Related Compound B RS, and USP Fluconazole Related Compound C RS in Solution A. Sonicate, if necessary, to dissolve. Standard solution: 0.01 mg/mL of USP Fluconazole RS in Solution A. Sonicate, if necessary, to dissolve.

Sample solution: Nominally 3 mg/mL of fluconazole from NLT 20 finely powdered Tablets in Solution A. Sonicate for 30 min with occasional swirling, prior to nal dilution. Pass through a suitable filter of 0.45-µm pore size.

5.1 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: 30°

Flow rate: 1 mL/min

Injection volume: 25 µL

5.2 System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0% for the fluconazole peak

5.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual unspecified impurity in the portion of Tablets taken:

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

r_U = peak response of any individual unspecified 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 = nominal concentration of fluconazole in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

a This is a process-related impurity, and monitored in the drug substance.

6 ADDITIONAL REQUIREMENTS

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

Change to read:

USP Reference Standards 〈11〉

USP Fluconazole RS

USP Fluconazole 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 Fluconazole Related Compound B RS

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

C₁₃H₁₃FN₆O _{(ERR 1-Oct-2024)}      288.28

USP Fluconazole Related Compound C RS

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

C₁₀H₈N₆          212.21