氟康唑USP32

1、Fluconazole C13H12F2N6O 306.271H-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 98.0 percent and not more than 102.0 percent of C13H12F

2、2N6O, calculated on the dried basis.Packaging and storage Preserve in tight containers, and store below 30. Labeling If a test for Related compounds other than Test 1 is used, then the labeling states with which Related compounds test(s) the article complies. USP Reference standards 11 USP Desacetyl

3、 Diltiazem Hydrochloride RS . 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 5 in 100 solution (w/v): the solution is clear and colorle

4、ss. Identification A: Infrared Absorption 197K. B: Ultraviolet Absorption 197U Solution: 200 µg per mL. Medium: alcohol. Loss on drying 731 Dry it at 105 for 3 hours: it loses not more than 0.5% of its weight. Residue on ignition 281: not more than 0.1%, determined on a 0.5-g sample. Iron 241 A

5、ccurately weigh 0.5 g of sample into a test tube. Dissolve in 5 mL of alcohol, add 5 mL of distilled water, and mix. The limit is 0.002%. Change to read: Related compounds NOTEOn the basis of information regarding the manufacturing process, perform either: (a) Test 1 or (b) Test 2 and Test 3.USP32 T

6、EST 1 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 Flucona

7、zole Related Compound C RS to a suitable volumetric flask, dissolve in acetonitrile, dilute quantitatively, and stepwise if necessary, with Mobile phase to volume, and mix to obtain a solution having known concentrations of 10 µg of each per mL. Test solution Transfer about 30 mg of Fluconazole

8、, accurately weighed, to a 10-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Chromatographic system (see Chromatography 621) 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

9、rate is about 0.5 mL per 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 4.9 minutes for fluconazole related compound A, 8.0 minutes for fluconazole related compound B,

10、 8.5 minutes for fluconazole related compound C, and 9.9 minutes for fluconazole; the resolution, R, between fluconazole related compound B and fluconazole related compound C is not less than 1.5; and the relative standard deviation of each peak for replicate injections is not more than 5.0%. Proced

11、ure Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into 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, fluconazo

12、le related compound C, and any other impurities in the portion of Fluconazole taken by the formula: 1000(C/W)(rU / rS)in which C is 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 Fluconaz

13、ole RS, respectively, in the Standard solution; W is the weight, in mg, of Fluconazole taken to prepare the Test solution; rU is the peak response obtained from the Test solution; and rS is the average peak response of fluconazole related compound A, fluconazole related compound B, fluconazole relat

14、ed compound C, or fluconazole obtained from replicate injections of the Standard solution: not more than 1.0% of any impurity with a relative retention time (RRT) of about 0.6 is found; not more than 0.2% of fluconazole related compound A or fluconazole related compound C is found; not more than 0.1

15、% of fluconazole related compound B is found; not more than 0.1% of any other individual impurity is found; not more than 0.3% of total unknown impurities is found; and not more than 1.5% of total impurities is found. TEST 2 Acetate buffer Prepare a 0.01 M anhydrous sodium acetate solution, adjust w

16、ith 1 N acetic acid to a pH of 5.0, and mix. Solution A: filtered and degassed Acetate buffer. Solution B: acetonitrile. Solution C: methanol. Mobile phase Use variable mixtures of Solution A, Solution B, and Solution C as directed for Chromatographic system. Make adjustments if necessary (see Syste

17、m Suitability under Chromatography 621). Diluent Prepare a mixture of Acetate buffer and methanol (84:16). Standard solution Dissolve an accurately weighed quantity of USP Fluconazole RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a know

18、n concentration of about 0.01 mg per mL. System suitability solution Dissolve suitable quantities of USP Fluconazole RS and USP Desacetyl Diltiazem Hydrochloride RS in Diluent. Dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution containing about 0.02 mg per mL and 0.0

19、06 mg per mL, respectively. Test solution Transfer about 200 mg of Fluconazole, accurately weighed, to a 100-mL volumetric flask, and dissolve in and dilute with Diluent to volume. Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 261-nm detector and a 4.0-m

20、m × 10-cm column that contains packing L1. The flow rate is 1 mL per minute. The chromatograph is programmed as follows. Time(minutes)Solution A (%)Solution B (%)Solution C (%) Elution01080515isocratic102080®305®5515linear gradient(A and B)2023305515isocratic232530®8055®515r

21、eset composition253080515re-equilibrationChromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are 1.0 for fluconazole and about 1.2 for desacetyl diltiazem; the resolution, R, between fluconazole and desacetyl diltiazem

22、hydrochloride is not less than 10.0; the column efficiency for fluconazole is not less than 30,000 theoretical plates; and the tailing factor, T, is not more than 1.4. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for re

23、plicate injections is less than 5.0%. Procedure Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of Fluconazole

24、taken by the formula: 10,000(ri / rS)(C/W)(1/F)in which ri is the peak response of each impurity obtained from the Test solution; rS is the peak response of fluconazole obtained from the Standard solution; C is the concentration, in mg per mL, of USP Fluconazole RS in the Standard solution; W is the

25、 weight, in mg, of Fluconazole taken to prepare the Test solution; and F is the relative response factor as determined from the following table. Relative Response Factor(F) Relative Retention Time(RRT)0.720.170.370.850.480.601.210.670.790.961.141.180.971.201.321.0all other peaksNot more than 0.1% of

26、 any individual impurity is found; and not more than 0.5% of total impurities is found. TEST 3 Adsorbent: 0.25-mm layer of chromatographic silica gel mixture. Test solution Dissolve an accurately weighed quantity of Fluconazole in methanol to obtain a solution containing approximately 50 mg per mL.

27、Standard solutions Dissolve an accurately weighed quantity of USP Fluconazole RS in methanol to obtain Standard solution A having a known concentration of about 1 mg per mL (2.0%). Quantitatively dilute portions of this solution with methanol to obtain Standard solution B and Standard solution C hav

28、ing known concentrations of about 0.1 mg per mL (0.2%) and 0.05 mg per mL (0.1%), respectively. Developing solvent system Prepare a mixture of chloroform, methanol, and ammonium hydroxide (80:20:1). Application volume: 10 µL. Spray reagent A Dissolve about 170 mg of silver nitrate in 100 mL of

29、water. Spray reagent B (Potassium iodoplatinate solution) Dissolve about 375 mg of chloroplatinic acid in 5 mL of 1 N hydrochloric acid. Dissolve about 5 g of potassium iodide in 50 mL of water, and store in a light-resistant container. Prepare a mixture of water, the potassium iodide solution, and

30、the chloroplatinic acid solution (20:9:1). Procedure Proceed as directed for Thin-Layer Chromatography under Chromatography 621. Spray the dry plate with Spray reagent A, and expose the plate to 365-nm UV light for 10 to 20 minutes. Dry the plate for 20 minutes between 80 and 90, then spray the plate with Spray reagent B. Allow the plate to dry. Examine the plate and compare the intensities of any secondary spots observed in the chromatogram of the Test solution with those of the principal spots in the chromatograms of the Standard solut