Fluconazol Bp

• British Pharmacopoeia Volume I & II
• Monographs: Medicinal and Pharmaceutical Substances
Fluconazole

General Notices

(Ph Eur monograph 2287)


C13H12F2N6O 306.3 86386-73-4
Action and use
Antifungal.
Ph Eur
DEFINITION
2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol.
Content
99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
AppearanceWhite or almost white, hygroscopic, crystalline powder.
Solubility
Slightly soluble in water, freely soluble in methanol, soluble in acetone.
It shows polymorphism (5.9).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison fluconazole CRS .
If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substanceseparately in the minimum volume of methylene chloride R, evaporate to dryness on a water-bath and record new spectra using the residues.
TESTS
Appearance of solution
The solution is clear (2.2.1) and colourless (2.2.2, Method II).
Dissolve 1.0 g in methanol R and dilute to 20 ml with the same solvent.
Related substances
Liquid chromatography (2.2.29).
Test solution Dissolve 0.100 g of thesubstance to be examined in the mobile phase, sonicate if necessary, and dilute to 10.0 ml with the mobile phase.
Reference solution (a) Dilute 5.0 ml of the test solution to 100.0 ml with the mobile phase. Dilute 1.0 ml of this solution to 10.0 ml with the mobile phase.
Reference solution (b) Dissolve 5 mg of fluconazole for peak identification CRS (containing impurity A) in the mobile phase,sonicate if necessary, and dilute to 10 ml with the mobile phase.
Reference solution (c) Dissolve 3.0 mg of fluconazole impurity B CRS in the mobile phase, sonicate if necessary and, dilute to 100.0 ml with the mobile phase.
Reference solution (d) Dissolve 2.0 mg of fluconazole impurity C CRS in the mobile phase and dilute to 20.0 ml with the mobile phase. To 1.0 ml of this solution add 1.0 mlof the test solution and dilute to 10.0 ml with the mobile phase.
Column:
• — size: l = 0.15 m, Ø = 4.6 mm;
• — stationary phase: octadecylsilyl silica gel for chromatography R1 (5 µm);
• — temperature: 40 °C.
Mobile phase acetonitrile R, 0.63 g/l solution of ammonium formate R (14:86 V/V).
Flow rate 1.0 ml/min.
Detection Spectrophotometer at 260 nm.
Injection 20 µl.
Run time3.5 times the retention time of fluconazole.
Identification of impurities Use the chromatogram supplied with fluconazole for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peak due to impurity A; use the chromatogram obtained with reference solution (c) to identify the peak due to impurity B and the chromatogram obtained with reference solution(d) to identify the peak due to impurity C.
Relative retention With reference to fluconazole (retention time = about 11 min): impurity B = about 0.4; impurity A = about 0.5; impurity C = about 0.8.
System suitability Reference solution (d):
• — resolution: minimum 3.0 between the peaks due to impurity C and fluconazole.
Limits:
• — impurity A: not more than 0.8 times thearea of the principal peak in the chromatogram obtained with reference solution (a) (0.4 per cent);
• — impurity B: not more than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.3 per cent);
• — impurity C: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (d) (0.1 per cent);
• — unspecifiedimpurities: for each impurity, not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);
• — total: not more than 1.2 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.6 per cent);
• — disregard limit: 0.1 times the area of the principal peak in the chromatogram obtained with reference...