Add the following:
Fluconazole
;)
1H-1,2,4-Triazole-1-ethanol,1-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-ylmethyl)-.
2,4-Difluoro-1¢,1¢-bis(1H-1,2,4-triazol-1-ylmethyl)benzyl alcohol [86386-73-4].
»Fluconazole contains not less than 98.5percent and not more than 101.5percent of C13H12F2N6O,calculated on the dried basis.
Packaging and storage—
Preserve in tight containers,and store below 30
.
.
USP Reference standards á11ñ—
USP Fluconazole RS.USP Fluconazole Related Compound A RS.USP Fluconazole Related Compound B RS.USP Fluconazole Related Compound C RS.
Clarity and color of solutions—
Dissolve sample in methanol to obtain a 5in 100solution (w/v):the solution is clear and colorless.
Identification—
A:Infrared Absorption á197Kñ.
B:Ultraviolet Absorption á197Uñ—
Solution:
200µg per mL.
Medium:
alcohol.
Loss on drying á731ñ—
Dry it at 105for 3hours:it loses not more than 0.5%of its weight.
for 3hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%,determined on a 0.5-g sample.
Iron á241ñ—
Accurately weigh 0.5g of sample into a test tube.Dissolve in 5mLof alcohol,add 5mLof distilled water,and mix.The limit is 0.002%.
Related compounds—
Mobile phase—
Prepare a mixture of water and acetonitrile (80:20).
System suitability solution—
Use the Standard solution.
Standard solution—
Transfer accurately weighed quantities of USP Fluconazole RS,USP Fluconazole Related Compound A RS,USP Fluconazole Related Compound B RS,and USP Fluconazole Related Compound C RSto a suitable volumetric flask,dissolve in acetonitrile,dilute quantitatively,and stepwise if necessary,with Mobile phaseto volume,and mix to obtain a solution having known concentrations of 10µg per mLof each Reference Standard.
Test solution—
Transfer about 30mg of Fluconazole,accurately weighed,to a 10-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 260-nm detector and a 4.6-mm ×15-cm column that contains 3.5-µm packing L1.The flow rate is about 0.5mLper minute.The column temperature is maintained at 40.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:typical retention times are about 4.9minutes for fluconazole related compound A,8.0minutes for fluconazole related compound B,8.5minutes for fluconazole related compound C,and 9.9minutes for fluconazole;the resolution,R,between fluconazole related compound Band fluconazole related compound Cis not less than 1.5;and the relative standard deviation of each peak for replicate injections is not more than 5.0%.
.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:typical retention times are about 4.9minutes for fluconazole related compound A,8.0minutes for fluconazole related compound B,8.5minutes for fluconazole related compound C,and 9.9minutes for fluconazole;the resolution,R,between fluconazole related compound Band fluconazole related compound Cis not less than 1.5;and the relative standard deviation of each peak for replicate injections is not more than 5.0%.
Procedure—
Separately inject equal volumes (about 20µL)of the Standard solution and the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentage of fluconazole related compound A,fluconazole related compound B,fluconazole related compound C,and any other impurities in the portion of Fluconazole taken by the formula:
1000(C/W)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Fluconazole Related Compound A RS,USP Fluconazole Related Compound B RS,USP Fluconazole Related Compound C RS,or USP Fluconazole RS,in the Standard solution;Wis the weight,in mg,of Fluconazole taken to prepare the Test solution;rUis the peak response obtained from the Test solution;and rSis the average peak response of fluconazole related compound A,fluconazole related compound B,fluconazole related compound C,or fluconazole obtained from replicate injections of the Standard solution:not more than 0.1%of any individual impurity is found;and not more than 0.3%of total impurities is found.
Assay—
Dissolve about 200mg of Fluconazole,accurately weighed,in 100mLof glacial acetic acid,and titrate with 0.1Nperchloric acid VS,using a suitable anhydrous electrode system.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 15.31mg of C13H12F2N6O.USP28
USP28
Auxiliary Information—
Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 828
Pharmacopeial Forum:Volume No.30(1)Page 103
Phone Number:1-301-816-8394