Fluconazole Tablets
DEFINITION
Fluconazole Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fluconazole (C13H12F2N6O).
IDENTIFICATION
•  The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
•  Procedure
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 stock solution:  1.0 mg/mL of USP Fluconazole RS dissolved in water, and diluted with Mobile phase to volume. Sonicate the solution, if necessary. [Note—The target ratio is about 5% water to 95% Mobile phase. ]
Standard solution:  0.2 mg/mL of USP Fluconazole RS in Mobile phase prepared from the Standard stock solution
Sample solution:  Weigh NLT 5 Tablets, and disperse in a suitable quantity of water. Sonicate the solution, if necessary. Add a sufficient quantity of Mobile phase, sonicate for 5 min, and shake for 30 min. Dilute with Mobile phase to volume to obtain a concentration between about 1 and 4 mg/mL, and mix. [Note—The target ratio is about 5% water to 95% Mobile phase. ] Centrifuge a suitable portion of the mixture. Filter and quantitatively dilute a portion of the supernatant with Mobile phase to obtain a solution of about 0.2 mg/mL of fluconazole.
Chromatographic system 
Mode:  LC
Detector:  UV 261 nm
Column:  3.9-mm × 150-mm; 4-µm packing L1
Flow rate:  1 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Column efficiency:  NLT 1100 theoretical plates
Tailing factor:  NMT 3.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of fluconazole (C13H12F2N6O) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP Fluconazole RS in the Standard solution (mg/mL)
CU== nominal concentration of fluconazole in the Sample solution (mg/mL)
Acceptance criteria:  90.0%–110.0%
PERFORMANCE TESTS
•  Dissolution 711
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, Mobile phase, and System suitability:  Proceed as directed in the Assay.
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 final 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.
Chromatographic system and System suitability:  Proceed as directed in the Assay, making any necessary modifications.
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the labeled amount of fluconazole (C13H12F2N6O) dissolved:
Result = (rU/rS) × (CS/L) × V × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== 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 C13H12F2N6O is dissolved.
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 final concentration of (L/900) mg/mL, where L is the Tablet label claim in mg.
Sample solution:  Pass a portion of the solution under test through a suitable filter.
Chromatographic system 
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 size:  50 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Column efficiency:  NLT 1000 theoretical plates
Tailing factor:  NMT 1.5
Relative standard deviation:  NMT 2.0%
Calculate the percentage of the labeled amount of fluconazole (C13H12F2N6O) dissolved:
Result = (rU/rS) × (CS/L) × V × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== 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 is dissolved.
•  Uniformity of Dosage Units 905: Meet the requirements
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.
•  USP Reference Standards 11
USP Fluconazole RS Click to View Structure
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Behnam Davani, Ph.D., M.B.A.
Senior Scientific Liaison
1-301-816-8394
(SM12010) Monographs - Small Molecules 1
711 Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison
1-301-816-8106
(GCDF2010) General Chapters - Dosage Forms
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3208
Pharmacopeial Forum: Volume No. 34(4) Page 932